Review Article Carbon Nanotubes Hybrid Hydrogels …downloads.hindawi.com/journals/bmri/2014/825017.pdfReview Article Carbon Nanotubes Hybrid Hydrogels in Drug Delivery: A Perspective

Review ArticleCarbon Nanotubes Hybrid Hydrogels in Drug DeliveryA Perspective Review

Giuseppe Cirillo12 Silke Hampel2 Umile Gianfranco Spizzirri1

Ortensia Ilaria Parisi1 Nevio Picci1 and Francesca Iemma1

1 Department of Pharmacy Health and Nutritional Sciences University of Calabria 87036 Arcavacata di Rende Italy2 Leibniz Institute for Solid State and Materials Research Dresden Postfatch 270116 01171 Dresden Germany

Correspondence should be addressed to Giuseppe Cirillo giuseppecirillounicalit

Received 22 April 2013 Revised 27 October 2013 Accepted 31 October 2013 Published 21 January 2014

Academic Editor Christine Dufes

Copyright copy 2014 Giuseppe Cirillo et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

The use of biologics polymers silicon materials carbon materials and metals has been proposed for the preparation of innovativedrug delivery devices One of the most promising materials in this field are the carbon-nanotubes composites and hybrid materialscoupling the advantages of polymers (biocompatibility and biodegradability) with those of carbon nanotubes (cellular uptakestability electromagnatic and magnetic behavior) The applicability of polymer-carbon nanotubes composites in drug deliverywith particular attention to the controlled release by composites hydrogel is being extensively investigated in the present review

1 Introduction

During the last few years the development of innovativedrug delivery devices for different therapeutic agents hasattracted the interest of many researchers Several studiesindeed report on the design synthesis and characterizationof novel materials to be employed as delivery systems inthe aim to improve the efficiency of a selected drug [1]An ideal drug delivery system (DDS) has to maximize theefficacy and the safety of the therapeutic agent deliveringan appropriate amount at a suitable rate and to the mostappropriate site in the body By this strategy it is possible toprolong the pharmacological activity reduce the side effectsand minimize the administration frequency resulting in anenhanced patient compliance [2]

The use of innovative approaches in drug delivery fieldis required by the need of carriers for new biologicaltherapeutic agents such as nucleic acids and proteins butalso by the pharmaceutical companies due to the upcomingpatent expirations and the consequent interest in the devel-opment of novel formulations The employed strategies toachieve alternative drug delivery involve biologics polymerssilicon-based materials carbon-based materials metals or

combinations of them and these materials can be structuredin microscale or more recently in nanoscale formats [3]

Nanomedicine has been defined as ldquothe monitoringrepair construction and control of human biological systemsat the molecular level using engineered nanodevices andnanostructuresrdquo [4] It consists of application of nanotechnol-ogy to the diagnosis prevention and treatment of diseasesand represents a useful instrument to understand specificunderlying disease molecular mechanisms [5]

Nanomaterials are promising technologies to detect anddiagnose cancer and infectious diseases in their early stagesand play a key role in drug discovery drug delivery andgeneprotein deliveryThis kind of innovativematerials is ableto interactwith subcellular structures in the humanbodywitha high specificity finding a potential clinical application asdrug targeting systems in the aim to reduce adverse effects[6]

Nanocarriers are able to release the active compounddirectly into cells overcoming the biological barriers anddiscriminating target pathological tissue from the healthyones [7]

Among the nanotechnologies polymeric hydrogels haveraised a remarkable and considerable interest [8] Hydrogels

Hindawi Publishing CorporationBioMed Research InternationalVolume 2014 Article ID 825017 17 pageshttpdxdoiorg1011552014825017

2 BioMed Research International

represent a class of hydrophilic and crosslinked polymericnetworks insoluble in water and characterized by the abil-ity to hold a large amount of biological fluids includingwater within the spaces available among the polymericchains The water holding capacity depends on the pres-ence of hydrophilic functionalities (amido amino carboxylhydroxyl groups etc) in polymer chains and the watercontent may vary from 10 to thousands of times of theweight of the dry polymer network [9] Moreover thesepolymeric materials present a good biocompatibility and aresuitable for applications inmedical and pharmaceutical fieldsincluding wound dressings contact lenses artificial organstissue engineering and drug delivery systems [10 11]

Hydrogels can be classified according to several parame-ters such as their natural or synthetic origin and the cross-linking nature [12]

Generally all polymeric gels are either synthetic (poly(ethylene glycol) (PEG) [13] poly (vinyl alcohol) (PVA)[14] poly (acrylic acid) (PAA) [15] polyacrylamide (PAM)[16] and poly (methyl methacrylate) (PMA) [17]) or natural(alginic acid [18] pectin [19] chitin and chitosan [20]dextran [21] agarose [22] and different derivatives of thesepolymers)

According to their cross-linking nature hydrogels canbe divided into two main classes permanent hydrogels inwhich covalent bonds between polymeric chains are formedduring the cross-linking reaction and physical hydrogels inwhich the cross-linking is due to the formation of physicalinteractions such as hydrogen bonding ionic interactionvan der Waals interactions and molecular entanglementamong the polymeric chains Hydrogels based on acrylicmonomers are included in the first class while gelatine andagar-agar hydrogels are examples of materials belonging tothe second category [23]

Some of these polymeric networks are able to exhibitphase transition and changes in their equilibrium state inresponse to external stimuli and are known as ldquostimuli-responsiverdquo or ldquosmartrdquo hydrogels [24] This kind of materialsfinds application in targeted drug delivery due to the capa-bility to respond to environmental factors including physicalchemical and biochemical stimuli Physical stimuli consistof temperature pressure light electric magnetic and soundfields while chemical or biochemical stimuli involve pHionic strength ions or specific molecular recognition events[25] Stimuli-responsive hydrogels can be classified on thebasis of the external stimuli type in thermosensitive pHsensitive and electrosensitive [26] as well as sensitive tolight pressure ionic strength and different molecules forexample enzymes and so forth [27] Different strategies havebeen developed to apply the external stimuli to the hydrogelsand the main approaches involve the use of suitable bufferedsaline (phosphate or potassium) for pH responsive materialsthe increase of the temperature by hot plate andor IRirradiation in the case thermo-responsive elements and theapplication of a voltage by appropriate inert electrodes forelectroresponsive materials In the latter case it is possible tostudy the response of the hydrogel by modulating the voltageaswell as the intensity of the current Specific example of thesematters have been treated below in this review

2 Carbon Nanotubes

Carbon nanotubes (CNTs) are huge cylindrical largemolecu-les consisting of a hexagonal arrangement of sp2 hybridizedcarbon atoms (CndashC distance is about 14 A) [28 29]

The wall of CNTs is composed of one or multiplelayers of graphene sheets thus it is possible to discriminatethesematerials in single-walled carbon nanotubes (SWCNT)formed by rolling up of a single graphene sheet and mul-tiwalled CNTs (MWCNTs) formed by rolling up of morethan one graphene sheet Both SWCNTs and MWCNTsare capped at both ends of the tubes in a hemisphericalarrangement of carbon networks called fullerenes warped upby the graphene sheet (Figure 1) The interlayer separation ofthe graphene layers of MWCNTs is approximately 034 nm inaverage each one forming an individual tube and the outerdiameter ranging from 25 to 100 nm while for SWCNTs thisvalue ranges from 06 to 24 nm SWCNTs are characterizedby a better defined wall and a smaller diameter that makethem suitable as drug carriers due to their quality controlOn the contrary MWCNTs may present defects in theirnanostructure resulting in a lack of stability that makes theirmodification easier [30]

The adopted synthetic procedure influences CNTs lengthand diameter and due to attractive van der Waals forcesSWCNTs and MWCNTs tend to pack together in ropes Theobtained bundles containmany nanotubes and are longer andwider than the original ones fromwhich they are formedThisphenomenon could be important from a toxicological pointof view [31 32]

In the past few years carbon nanotubes have foundapplications in different fields including nanoelectronics andnanocomposite due to their considerable electrical mechan-ical and chemical stability but only in the recent periodthe interest was focused on their potential application asbiomedical devices [33 34]

Several research studies indeed focuses on the use ofcarbon nanotubes in biological systems [35 36] Balavoineet al used MWNTs for helical crystallization of protein [37]Mattson et al reported on the first application of carbon nan-otube technology to neuroscience research developing newapproaches for the growth of embryonic rat-brain neuronson MWNTs [38] and Sadler and coworkers immobilizedbiological species on both SWNTs and MWNTs for potentialbiosensor and bioreactor systems [39]

The employment of CNTs as drug excipients with lowtoxicity and immunogenicity is also largely investigated [40]The ability of carbon nanotubes to release drugs was studiedin the aim to obtain innovative drug vehicles to be applied inthe field of nanomedicine [41]

Different types of therapeutic molecules have beenreported to be delivered by CNTs recording better resultsthan that obtained with conventional vehicles [42ndash44] Thehigh surface area of CNTs indeed allows us to achieve ahigh loading capacity of chemotherapy drugs [45] MoreoverCNTs loaded with drugs can extravasate in tumor tissuesover time because of the enhanced permeability and retentioneffect of solid tumors [46]

BioMed Research International 3

Graphene sheet

Warping

Fullerene

Rolling

Capping

SWCNT

Figure 1 Molecular structures of SWCNT and MWCNT

The remarkable importance of carbon nanotubes inbiomedical field is related to their ability to undergo cellinternalization Nonetheless the molecular mechanism ofthe interaction between CNTs and cellstissues has to beexplained

Kam et al [47 48] propose that SWNTs traverse thecellular membrane via endocytosis whereas Pantarotto etal [49] suggest a nonendocytosis mechanism involving theinsertion and diffusion of nanotubes through the lipid bilayerof the cell membrane Several studies showed that highamounts of CNTs can be found in the cell matrices andin the nucleus after exposure to these nanomaterials [50]This represents a starting point for the development of novelbiomedical devices based on CNT nanostructure

Regarding the drug delivery field three differentmethodsof interaction between CNTs and active compounds havebeen proposed the first one is a porous absorbent to entrapactive components within a CNT mesh or CNT bundle thesecond approach is through functional attachment of thecompound to the exterior walls of the CNTs and the last oneinvolves the use of CNT channels as nanocatheters

Water solubility is an important prerequisite for gas-trointestinal absorption blood transportation secretion andbiocompatibility thus CNT composites involved in ther-apeutic delivery system have to present this requirementSimilarly it is important that such CNT dispersions shouldbe uniform and stable in a sufficient degree so as to obtainaccurate concentration data The solubilization of pristineCNTs in aqueous media is one of the key obstacles in theway for them to be developed as practical drug carriers owingto the rather hydrophobic character of the graphene sidewalls coupled with the strong 120587-120587 interactions between theindividual tubesThese properties cause aggregation of CNTsinto bundles [51]

In order to achieve a successful dispersion of carbonnanotubes the medium should be capable of both wettingand modifying the hydrophobic tube surfaces in the aimto decrease tubersquos bundle formation Foldvari and Bagonlurihave proposed four different strategies to obtain desirabledispersion [30] (1) surfactant-assisted dispersion (2) sol-vent dispersion (3) functionalization of side walls and(4) biomolecular dispersion Among the above described

approaches functionalization has been the most effectiveapproach In addition functionalization has been showncapable of decreasing cytotoxicity improving biocompatibil-ity and giving opportunity to appendage molecules of drugsproteins or genes for the construction of delivery systems[40]

Furthermore the CNT functionalization is of dramaticimportance from a toxicological point of view

As cited before CNTs have the ability to be cytotoxic bothin vivo and in vitro [52ndash54]This is due to both the structuraland physiochemical aspects of CNTs As the particle sizeof a material decreases indeed there is a correspondingelevation in reactivity and hence toxicological and inflam-matory potential [55] This is because nanomaterials such asCNTs have relatively high surface area to volume ratios overwhich more chemical interactions can occur Furthermorenanomaterials share similar dimensional scales to many largebiological molecules rendering them inherently more likelyto disrupt natural interactions and cause toxicity [56 57]

CNTs have demonstrated both positive [58] and negative[59] toxicological effects and that the mechanisms regulatingtheir toxicity are still to be understood [60]

CNTs are believed to present the highest risk of adversehealth effects to the respiratory system due to their lightweight and propensity to be aerosolized and inhaled In 2004Lam et al showed CNTs to cause granulomas in the lungtissue of mice as a result of intratracheal instillation [59]Increasing doses corresponded to higher rates of inflam-mation and prominence of lesions When compared to thequartz positive control a known cause of granulomas andlung lesions CNTs showed a higher incidence of negativehealth effectsThis included increased inflammation fibrosisgranulomas necrosis and lethality Similar results have beendemonstrated repeatedly [61] Comparing more directly toasbestos in which the mesothelium of the lungs is affectedPoland et al exposed the mesothelial tissue lining thelungbody cavity of mice to CNTs with a median lengthof approximately 20120583m [62] Toxic behavior was evidencedincluding inflammation and the formation of granulomas

Although a significant number of studies have been pub-lished regarding the activation of immune cells by CNTs veryfew have focused on the immunogenicity of CNTs themselves


[63] Although it had been described for C60 fullerenederivatives [64] the induction of anti-CNT antibodies hasnot been evidenced so far even when injected to mice in thepresence of a strong immune adjuvant [65]

The biopersistence of CNTs warrants additional concernswhen considering them for biological uses particularly sincethis validates their comparison with the carcinogen asbestosWhile this is concerning the in vivo study of mice hasdemonstrated that ldquopristinerdquo CNTs have a relatively low half-life of 3 hours in the bloodstream [66] Through the use ofvarious imaging techniques the in vivo study ofmice has alsoshown that CNTs pose risks specifically to the lungs liverand spleen persisting in these locations at up to 10 of theinitial dose at the studies completion time of 28 days [67]Furthermore it is possible that the toxicological behavior ofCNTs activates at a certain threshold meaning that this acti-vation barrier would need to be identified and further dosageof CNTs limited according to the biopersistence [68] Biop-ersistence depends on the functionalization CarboxylatedCNTs can be degraded not only in vitro using a model plant-derived enzyme the horseradish peroxidase [69 70] butalso by the more physiologically relevant myeloperoxidase(MPO) present within granulocytes (mainly neutrophils) andto a lesser extent within macrophages [71] Importantly theMPO-degraded CNTs did not generate inflammation whenaspirated into the lungs of mice [72]

3 CNTs-Hydrogel Hybrid Materials

As reported before hydrogels have emerged as promising bio-materials due to their unique characteristicsThese polymericnetworks indeed resemble living tissues closely in theirphysical properties because of their relatively elastomeric andsoft nature and high water content minimizing mechanicaland frictional irritation These materials show a minimaltendency to cell adhesion and to absorption of proteins frombody fluids due to their very low interfacial tension Inaddition the swelling capacity allows to easily remove reagentresidues [73 74]

Unfortunately the same water content which makeshydrogels such a special class of materials is also responsiblefor their biggest disadvantage the poor mechanical proper-ties Hydrogels with improved mechanical properties couldbe obtained through the preparation of interpenetratingpolymer networks (IPN) by chemical cross-linkingHoweverthe presence of residual cross-linking agents could lead totoxic side effects [75]

Burst or incomplete release of the therapeutic agent andthe poor scalability of the manufacturing process representother limitations in the use of hydrogel as drug deliverysystems In the aim to overcome these drawbacks hydrogelcompositesmaterials have been developed [76]The synthesisof these materials involves the incorporation of nanoparticlesinto a hydrogel matrix enhancing mechanical strength drugrelease profile remote actuation capabilities and biologicalinteractions [77] The development of novel nanocompositehydrogels was encouraged by the recent advances in thechemical physical and biological fields combined with risingneeds in the biomedical and pharmaceutical sectors Novel

polymer chemistries and formulations as well as fabricationand processing techniques are supported by improved instru-mentation that can measure and manipulate matter at thenanoscale level [78]

Hydrogel nanocomposites with different particulatesincluding clay gold silver iron oxide carbon nanotubeshydroxyapatite and tricalcium phosphate have been synthe-sized and characterized to evaluate their potential applicationas biomaterials [79]

In 1994 the first polymer nanocomposites using carbonnanotubes as filler was reported [80] In earlier nanocom-posites nanoscale fillers such as carbon blacks silica claysand carbon nanofibers (CNF) were employed in the aim toenhance the mechanical electrical and thermal propertiesof polymers [81] In the last years carbon nanotubes havereceived much attention as suitable materials to enhance theelectrical and mechanical properties of polymers [82]

The technology implications of using CNTs-hydrogelare significant to many fields from semiconductor devicemanufacturing to emerging areas of nanobiotechnologynanofluidics and chemistry where the ability to moldstructures with molecular dimensions might open up newpathways to molecular recognition drug discovery catalysisand molecule specific chemobiosensing [83]

Based on these considerations the identification of themost effective synthetic strategy to prepare CNTs-hydrogelhybrid materials has been aroused by an increased andconsiderable interest

The adopted synthetic approaches can be classified intocovalent and noncovalent functionalization of carbon nanos-tructures with polymeric materials The structure of CNTs inthe final composite represents the main difference betweenthese two strategies In the noncovalent approach nomodifi-cation of the CNT structure occurs thus the properties of thewhole composite are determined by the intrinsic propertiesof the starting CNT materials in the covalent approach asignificant modification of the CNT surface is performed andit is responsible of the composite final properties

The noncovalent functionalization approach is basedon the molecular composition of CNTs The sp2 bondedgraphene structures at the sidewalls of CNTs indeed containhighly delocalized p electrons which can form functionalizedCNTs with other p electron-rich compounds through 120587-120587interaction This organic functionalization method avoidsmodifying the intrinsic structures of CNTs and gives struc-turally intact CNTs with functionalities Recently the poten-tial interaction between the highly delocalized 120587-electrons ofCNTs and the 120587-electrons correlated with the lattice of thepolymer skeleton has generated much interest and providedthemotivation for studying the optical and electronic proper-ties of composites of CNTs and 120587-conjugated polymers [84]

The main strategies for the synthesis of CNTs-polymercomposites by covalent functionalization consist of ldquograftingtordquo and ldquografting fromrdquo approaches [85 86]

The first method involves the reaction of preformedpolymeric chains with the surface of either pristine orprefunctionalized carbon nanotubes by performing radicalor carbanion additions as well as cycloaddition reactions tothe CNT double bonds Since the curvature of the carbon


nanostructures imparts a significant strain upon the sp2hybridized carbon atoms that make up their frameworkthe energy barrier required to convert these atoms to sp3hybridization is lower than that of the flat graphene sheetsmaking them susceptible to various addition reactionsTherefore to exploit this chemistry it is only necessary toproduce a polymer centered transient in the presence ofCNT material Otherwise the presence of defect sites onthe surface of oxidized CNTs as opened nanostructureswith terminal carboxylic acid groups allow covalent linkagesof oligomer or polymer chains The ldquografting tordquo approachonto CNT defect sites involves the reaction of the functionalgroups on the nanotube surfaces with the reactive end groupsonto a readymade polymer For this purpose preformedcommercial polymers of controlled molecular weight andpolydispersity can be employed The main limitation of thistechnique is that initial binding of polymer chains stericallyhinders diffusion of additional macromolecules to the CNTsurface leading to a low grafting density

The ldquografting fromrdquo approach involves the polymeriza-tion of monomers from surface-derived initiators on CNTsThese initiators are covalently attached using the variousfunctionalization reactions developed for small moleculesincluding acid-defect group chemistry and side-wall func-tionalization of CNTs The polymer growth is not limitedby steric hindrance thus this synthetic strategy allowsus to obtain efficiently grafted polymers characterized bya high molecular weight In addition nanotube-polymercomposites with quite high grafting density can be preparedHowever an accurate control of the amounts of initiator andsubstrate and of the polymerization reaction conditions isrequired by this methodology Moreover the continuous 120587-electronic properties of CNTs would be destructed by theacid oxidation even worse CNTsmay be destroyed to severalhundred nanometers in length As a result compared withthe ldquografting fromrdquo the ldquografting tordquo has much less alterationof the structure of CNTs [87 88]

Many techniques including esterification [89] ldquoclickrdquochemistry [90] layer-by-layer self-assembly [91] pyrenemoi-ety adsorption [92 93] radical coupling [94 95] anionic cou-pling [96] radical polymerization [97] supercritical CO

2-

solubilized polymerization or coating [98] 120574-ray irradiation[99] cathodic electrochemical grafting [100] polyconden-sation [101 102] reversible addition fragmentation chain-transfer (RAFT) polymerization [103 104] anionic poly-merization [105] ring-opening polymerization [106 107]and atom transfer radical polymerization (ATRP) [108 109]have been employed in the aim to functionalize CNTs withpolymers

31 CNTs-Hydrogels in Drug Delivery All the above men-tioned considerations clearly highlight the importance andthus the considerable interest of the scientific community tothe use of composite materials based on carbon nanotubesand polymeric hydrogels to be applied as innovative drugdelivery devices

Nanohybrid hydrogels indeed combine properties ofboth hydrogels and CNTs carrying out the preparation of

devices with improved physic-chemical mechanical andbiological properties [110]

For tissue regeneration CNTs have been blended withboth synthetic [111] and biological [112] tissue scaffolds in theaim to improve their mechanical properties andor electricalconductance [113]

The ability of CNTs to lower the impedance of polymermatrices may be useful for the subset of tissues wherebyelectrical signals are propagated namely neural tissue andcardiac muscle CNTs have been demonstrated to be ableto improve neural signal transfer while supporting dendriteelongation and cell adhesion [114] and the electrical con-ductivity of CNTs could be a useful tool for directing cellgrowth as shown for the case of osteoblast proliferation inwhich electrical stimulation delivered through novel cur-rent conducting polymernanophase composites promotesosteoblast functions that are responsible for the chemicalcomposition of the organic and inorganic phases of bone[115] Furthermore application of electrical stimulation onthe conducting matrix could be used to increase the rate ofneurotrophin release to augment nerve regeneration [112]

In addition to neural cells and osteoblasts CNT compos-itematrices have also been shown to be useful scaffolds for theadhesion and the long-term growth of a variety of other celltypes ranging from skin fibroblasts [116] tomuscle myoblasts[117]

CNTs were wrapped with various polysaccharides to sys-tematically investigate the effect of hydrophilicityhydropho-bicity and surface chemistry on cell behavior It was foundthat amylase-wrapped surfaces presenting OH groups wereoptimal to promote cell adhesion and viability [118] CNTscovalently functionalized with phosphonate and sulfonategroups were able to nucleate hydroxyapatite (HA) andundergo mineralization indicating their promise as a bonescaffold [119] Differences in the surface chemistry andfunctionality of CNT substrates were also shown to affectosteoblast cell phenotype [120]

Among polysaccharides chitosan is widely employedto prepare CNTs-hydrogels A research study indeed wasreported on the synthesis of chitosan hydrogel beads impreg-nated with carbon nanotubes (CNTs) Composite hydrogelbeads were manufactured by dispersing CNTs (001 wt)with cetyltrimethylammonium bromide (005wt) into chi-tosan solution (1 wt) andmechanical strength acid stabilityand adsorption capacity to the anionic dye Congo red of theprepared materials were investigated Maximum endurableforce at complete breakdown of hydrogel beads increasedfrom 187 to 762N with incorporation of CNTs and itsadsorption capacity increased from 17832 to 42334mg gminus1for adsorption of Congo red [121]

Carbon nanotubes were also incorporated into gellangum hydrogels as conducting fillers to achieve an electricallyconducting hydrogel for electrical cell stimulation The for-mation of hydrogels involves a conformational change fromthe disordered (random coil) to ordered (double helix) chainstructure on cooling followed by aggregation of helices toform a gel network in the presence of a sufficient crosslinker(cations) concentration CNTs were incorporated by probesonication and percolation studies revealed that a carbon


nanotube concentration of 13 by weight is required toachieve electrical conduction through the hydrogel [122]

In another work molecularly imprinted polymers (MIPs)suitable for the electroresponsive release of diclofenac sodiumsalt drug were synthesized by precipitation polymerizationin the presence of carbon nanotubes (CNTs) [123] by amodified grafting approach [124] Conventional and elec-troresponsive imprinted polymers were synthesized withmethacrylic acid as the functional monomer and ethyleneglycol dimethacrylate as the crosslinker In vitro releaseexperiments performed in aqueous media highlighted theability of the MIPs and spherical imprinted polymers dopedwith CNTs to release the loaded template in a sustainedmanner over time in comparison to that of the correspondingnonimprinted materials

In another study CNTs were tested as reinforcing agentfor polyvinyl alcohol (PVA) hydrogels and the resultingcomposite material was found to elicit a stronger biolog-ical response than pure hydrogel in osteochondral defectrepairing application An increase in bone growth rate atthe implanttissue interface was detected as a result ofthe increasing concentration of calcium and phosphorusin the implants over time without any kind of significantinflammatory process after 12 weeks [125]

Specifically the effect of MWNTs on the mechanicalproperties of hydrogels was also tested by preparing acompositematerial containing poly(vinyl alcohol) (PVA) andpoly(vinyl pyrrolidone) (PVP) with wrapped multiwalledcarbon nanotube (MWCNT) The results demonstrated thatthe mechanical properties of the composite hydrogel wereimproved significantly by adding MWCNTs Particularly a133 improvement of the tensile strength and a 63 improve-ment of the tear strength were achieved by the addition ofonly 10 wt of MWCNTs In addition all the MWCNT-PVPPVA composite hydrogels became more wear-resistantin the presence of PVP with different MWCNT contents[126]

Different composite scaffolds composed of hydroxyap-atite (HAp) and collagen were synthesized by an in situprecipitation method The obtained scaffolds showed highermechanical performance than pure collagen scaffold andhierarchical porosity and thus was regarded as a promisingroutine for bone regenerative application [127]

Inclusion of carbon nanotubes in polymeric hydrogelsincreases conductivity and decreases transition time Specif-ically the effect of CNTs on hydrogels prepared by simplefree-radical copolymerization of commercially purchasedmonomers such as sodium acrylate sodium (4-styrenesulfonate) and polyethylene glycol diacrylate physicallycrosslinked by means of metal ions was explored Theused metal ions are the Fe2+Fe3+ redox couple due to itsability to control the degree of cross-linking in a polymerbearing hard carboxylate side groups Iron ions in differentoxidation states indeed have distinct coordination prefer-ences and Fe3+ binds more strongly than Fe2+ to ldquohardrdquoligands Thus the change in oxidation state can be used tomodulate the cross-linking and the mechanical properties ofthe bulkmaterial by the interconversion of Fe2+ and Fe3+The

conductivity of the hydrogel was improved by the addition of1minus3 vinyl-functionalized MWNTs and as result the chargeversus time response changed dramatically The time to pass40 Coulombs decreased from 119 h for hydrogel with nonanotubes to 32 h for 3 MWNTs Thus the nanotubesimprove conduction such that the distance that iron atomsmust diffuse for reduction is decreased [128]

The same effect was recorded in nanotube-polymericionic liquids gels synthesized by noncovalent functional-ization of oxidized single-walled carbon nanotube surfaceswith imidazolium-based poly (ionic liquids) (PILs) using insitu radical polymerization method The obtained hydrogelwas characterized by high thermal stability with the onsetpoints of decomposition shifting to a higher temperaturewith increasing SWNT contents in the gel composites Byplotting the surface resistivity with respect to the loadingcontent of SWNT in SWNT-PIL gel composites a decreasein surface resistivity of gel composite (from 38 times 107 to 17 times103Ωsquare) with an increase in the SWNT contents (from0 to 15 wt) was recorded [129]

MWNTs were also found to significantly enhance thespecific surface areas (280ndash400m2g) the thermal stabilityand electrical conductivities (12ndash69sdot10minus2 Scm) of compositeaerogels prepared by embedding carbon nanotubes intopoly(34-ethylenedioxythiophene)mdashpoly(styrenesulfonate)(PEDOT-PSS) supermolecular hydrogels in the presence of avery small amount of PVA In this work CNTs could be bothin the pristine and in the oxidized state (by means of acidictreatment) while PVA is used to keep from aggregation ofMWCNTs and hydrogels are synthesized by polymerizing34-ethylenedioxythiophene with excessive ferric nitrate asoxidizing agent as well as cross-linking agent in the presenceof poly(sodium 4-styrenesulfonate) [130]

Similarly multiwalled carbon nanotubes were chemicallymodified with ethylene glycol to improve their dispersionin poly(34-ethylene dioxythiophene)-poly(4-styrenesulfo-nate) It was found that the functionalized CNTs welldispersed in the composite material formed a conductivenetwork after spray-coatingThe surface resistance and trans-mittance of the films decreased as the number of coatingsincreased The surface resistance of the films was furtherdecreased with the addition of polar solvents while thecurrent remarkably increased It was noted that polar solventshaving a high dielectric constant led to stabilization andhigh dispersity of the negative charged CNTs and provided ascreening effect between the polymeric counterpart resultingin an increase of the electric and electrochemical properties[131]

High-quality conductive composite hydrogels composedof SWNTs polypyrrole (PPy) and poly(ethylene glycol)diacrylate (PEGDA) hydrogel were successfully preparedthrough interfacial polymerization (IP) Compared to theconventional sequential interpenetrating polymerization(CI) IP is able to better improve the electricalelectrochemi-cal properties of the incorporated hydrogel due to thehigher content of PPy up to 141 wt in its dry weight Theelectrical conductivity of PPyPEGDA hydrogel is nearlymore than two orders of magnitude higher than that of the


hydrogel prepared via CI In particular the electron-transferresistance (Rct) dramatically decreased from 9320U forthe pure hydrogel to 247U for the SWNTPPyPEGDAhydrogel It was also found that the addition of SWNTsand PPy would not noticeably decrease the swelling ratiowhile significantly improving the mechanical and electricalproperties of the pure PEGDA hydrogel The compositehydrogel effectively integrates the remarkable electricalelectrochemical properties from SWNTs and PPy withexcellent biocompatibility from the hydrogel [132]

The importance in retaining of the typical swellingproperties of hydrogels was highlighted in a work in whichsingle-walled carbon nanotubes were incorporated into apoly(ethylene glycol) (PEG) hydrogel by covalent bonds Inparticular SWNTs were functionalized with poly(ethyleneglycol) methacrylate (PEGMA) to obtain water-soluble pegy-lated SWNTs (SWNT-PEGMA) and then the functionalizedSWNTs were covalently bonded through their PEG moietiesto a PEG hydrogel The hybrid network was obtained fromthe cross-linking reaction of poly(ethylene glycol) diacrylateprepolymer and SWNT-PEGMA by dual photo-UV andthermal initiations and their swelling properties were foundto be maintained when compared with the native PEGhydrogel [133]

In another research study the influence of CNTs onswelling behavior and wettability was studied by preparinga hybrid structure of aligned carbon nanotubes and a pH-responsive hydrogel The composite was prepared by per-forming a chemical vapor deposition of a P(MAA-co-EGDA)hydrogel directly on carbon nanotube arrays with low sitedensity frommonomer vaporsTheprocess allowed preserva-tion of the monomer functionality retention of the nanotubealignment and control of the coating thickness at the sub-100 nm levelThe P(MAA-co-EGDA) hydrogel demonstratedpH-responsive swelling on both planar surfaces and carbonnanotube arrays and no appreciable swelling was recordedwhen immersing the hydrogel in acidic solutions A swellingratio of 38 defined as the thickness increase relative to thedry thickness was observed at pH 7 indicating the ionizationof carboxyl groups in the P(MAA-co-EGDA) hydrogel At thesame time the coated nanotube arrays showed a smoothersurface due to the expansion of the hydrogel The hydrogelcoating significantly enhanced the wettability of the CNTsurface The wettability of the coated VACNTs depended onboth the coating thickness and the pH conditions At pH2 the wettability of the coated CNTs with different coatingthicknesses was in agreement with the calculated results ofthe Cassie-Baxter model Under neutral pH conditions thecoated VACNT surface exhibited an apparent contact angleof nearly zero The superwettability was attributed to thesynergistic effect of the structure porosity and the ionizationof the pH-responsive hydrogel [134]

The influence of CNTs on cyclodextrins-based hydrogelwas also matter of studies in several articles

Chemically responsive supramolecular SWNT hydro-gel was prepared by using soluble SWNTs functionalizedcyclodextrin moieties on SWNT surface Since cyclodextrinshows high solubility inwater water-soluble SWNTs carryingcyclodextrin are obtained by using 120587-120587 interaction between

pyrene modified cyclodextrin and SWNTs Cyclodextrinforms host guest complexes with various kinds of guestcompounds thus vacant cavities in the composite are ableto capture guest molecules on SWNT surface [135]

In another work poly(ethylene glycol)-grafted-multiwal-led carbon nanotube (MWNT-g-PEG) was synthesized bya coupling reaction and formed inclusion complexes afterselective threading of the PEG segment of the MWNT-g-PEG through the cavities of 120572-cyclodextrins units Thecomplexation of the PEG segments with cyclodextrin andthe hydrophobic interaction between the MWNTs resultedin the formation of supramolecular hybrid hydrogels with astrong network Thermal analysis showed that the thermalstability of the hydrogel was substantially improved by up to100∘C higher than that of native hydrogel The mechanicalstrength of the hybrid hydrogels was also greatly improved incomparison with that of the corresponding native hydrogelsThe resultant hybrid hydrogels were found to be thixotropicand reversible and could be applied as a promising injectabledrug delivery system [136]

CNT was hybridized into a supramolecular hydrogelbased on the selective inclusion of 120572-cyclodextrin ontopoly(ethylene oxide) (PEO) segments of a triblock copoly-mer that is PEOblock-poly(propylene oxide)-block-PEOThe network density of hydrogel was designedly reduceddecreasing the content of 120572-cyclodextrin in order to improvethe diffusion of encapsulated substances while CNT playeda key role in mechanical reinforcement resulting in theincrease of storage modulus In addition the incorporationof CNT could decrease the gelation time and the CNThybridized hydrogel still kept the shear-thinning propertyCell viability assays confirmed the equivalent cytotoxicity ofthe supramolecular hybrid hydrogels to that of the nativehydrogels without CNT Consequently the synthesized CNT-hybridized supramolecular hydrogel shows a great potentialfor biomedical applications [137]

In the literature several studies aim to evaluate theeffect of introducingCNTs into polyacrylamide-based hydro-gels Different hydrogels synthesized by using acrylamideas monomer and methylenebisacrylamide andor tetram-ethylethylenediamine as crosslinkers were prepared by freeradical cross-linking copolymerization in water [138 139]Similarly the corresponding composite materials were pre-pared by introducing MWNTs into the polymerization feedat different amount () ranging from 01 to 15 and 50[83]

It was observed that high MWNT content compositesdry much faster as the result of having larger desorptioncoefficients for all measurements while a slower swelling isrecorded because of a smaller diffusion coefficients of solventin the polymeric network [138]

The mechanical properties of MWNT-polymer compos-ites were found to be highly dependent on nanotube disper-sion which directly influences the molecular tube-tube andtube-polymer interactions in the composites Suchmolecularinteractions will play a critical role in load transfer andinterfacial bonding that determines mechanical properties ofthe materials The variations in the nanotube dispersion inthe resultant composite could be the major reason for this


phenomenon while the increasingMWNT content producesinfinite network reducing the swelling and decreasing com-pressive elastic modulus [139]

Regarding the electrical properties the addition of carbonnanotubes to polymer systems with an isolator characterleads to the formation of electrically conducting compositestructures For this purpose CNT addition has to exceed acritical value [83]

The effect of CNT addition on thermally responsivehydrogels was shown in the following reported studies [140141]

Reversible thermally and optically responsive actuatorswere prepared utilizing composites of poly(N-isopropylacry-lamide) (pNIPAM) loaded with single-walled carbon nan-otubes Uniform SWNT dispersion in the p-NIPAM hydro-gels was achieved by means of sodium deoxycholate solutionas surfactant With nanotube loading at concentrations of075mgmL authors demonstrated up to 5 times enhance-ment to the thermal response time of the nanotube-pNIPAMhydrogel actuators caused by the enhanced mass transport ofwater molecules Additionally the ability to obtain ultrafastnear-infrared optical response in nanotube-pNIPAM hydro-gels under laser excitation enabled by the strong absorptionproperties of nanotubes was shown [140]

A nanocomposite of multiwalled carbon nanotubes andtemperature responsive N-isopropylacrylamide hydrogelswas prepared by using Tetra (ethylene glycol) dimethacrylateas crosslinker in a radical polymerization method Vari-ous amounts of acrylamide (AAm) were added to modu-late the lower critical solution temperature (LCST) of thenanocomposites for tailored physiological applications Anincrease in the amount of AAm shifted the LCST transitionto higher temperatures while the addition of nanotubescontributed to interesting properties including tailorabilityof temperature responsive swelling and mechanical strengthof the resultant nanocomposites The addition of MWC-NTs significantly decreased the swelling ratios due to thehydrophobic behaviour while it did not affect the LCSTtransition temperature range [77]

Hybrid composite hydrogels were also synthesized byusing gelatin as starting materials and the effect of CNTson the swelling properties of the resultant materials wasevaluated The choice of gelatin is of great importance byvirtue of its advantageous physical chemical and biologicalproperties which allow us a wide range of applications infood science biomedical and pharmaceutical field [141ndash143]

In particular a hybrid gelatin hydrogel with carbonnanotubes was synthesized by physical mixing method andstudied in terms of water affinity behavior Within the first5min the swelling ratio of hybrid gel was higher than thatof native gelatin gel due to the capillarity of MWNTs in thematrix which is help for the solvent diffusing into the gelmatrix After this time interval the hybrid gel was slowerto reach swelling equilibrium than that of pure gelatin gelThis indicated that MWNTs are able to inhibit the swellingof gel matrix by inhibiting the dissolution of gelatin in thematrix This effect of MWNTs can be called a shieldingeffect and it represents the leading effect after the first 5min[35]

The increase in the electroconductivity of gelatin contain-ing hybrid hydrogels was also proved andmultiwalled carbonnanotube (MWNTs)gelatin composites were prepared bydispersion ofMWNTs through ultrasonication in an aqueousmedium in the presence of sodium dodecyl sulfate as anionicsurfactant The response of the composite and pure hydrogelto the applied electrical field was investigated Both thecomposite and pure hydrogel showed a two-stage bendingphenomenon an early bending towards the anode and alater bending towards the cathode The incorporation ofMWNTs gradually decreased the swelling of the hydrogel andexerted no effect on the swelling mechanism which followedthe second order kinetic The bending mechanism can beexplained on the osmotic pressure difference at the solutiongel interface Bending towards the anode at the first stageis attributed to the accumulation of the positive ions at theanode side of the gel film in the solution The accumulatedions created osmotic pressure difference at the anode sideThe osmotic pressure difference causes more water to pen-etrate into gel at the cathode side than the anode side leadingthe gel to bend towards the anodeThe later bending towardsthe cathode may be attributed to the diffusion of the positiveions into the gel which creates an osmotic pressure differenceon the cathode side of the gel The composite showedgood reversible behavior compared to the gelatin whichmight be due to the condensed structure of the compositecompared to the gelatin which erodes to a great extent onexposure to DC current for longer time Both the bound andunboundwater contents (determined by differential scanningcalorimetry) decreased with the addition of MWNTs Thisphenomenon might be due to the hydrophobic effect of theMWNTs and increase in cross-linking density between theMWNTs and gelatin by increasing theMWNT concentration[144]

In a different work authors designed synthesized andcharacterized electroresponsive composite microgels to beinserted into a suitable topical drug delivery device in orderto release diclofenac sodium salt therapeutics as consequenceof an applied external voltage [145] The hybrid hydrogelscomposed of gelatin and multiwalled carbon nanotubes weresynthesized by a modified grafting approach and employ-ing an emulsion polymerization method in the presenceof sodium methacrylate and N1198731015840-ethylenebisacrylamideDifferent amounts of nanotubes (up to 35 by weight) werecovalently inserted into the polymeric network in orderto determine the percentage conferring the highest electricsensitivity to the composite microspheres (Figure 2) Theswelling properties of microgels confirm the polyelectrolytebehavior of hydrogels and the application of an externalelectric field (at pH 74) caused a reduction of the swellingdegree from 1350 to 420 as a consequence of a built-inosmotic pressure Drug release experiments demonstratedthe ability of the most responsive composite to controldiclofenac sodium salt release over time The electric stim-ulation resulted in a further increase of the release (+20) inMWNTs containing materials

Similarly to the gelatin hydrogels Fmoc-protected aminoacid based hydrogel has been used to incorporate and dis-perse functionalized single-walled carbon nanotube within


NaMAEBA

Initiator system

MWNT

MWNT GL-NTx

Gel

Ultrasonication

Figure 2 Synthesis of electroresponsive gelatin hybrid microgels

the gel phase to make a hybrid hydrogel a more stable elasticand conductive material than the native gel [146]

An electro-responsive transdermal drug delivery systemwas prepared by electrospinning of poly(vinyl alcohol)poly(acrylic acid)multiwalled carbon nanotubes (MWCNTs)nanocomposites The surface modification of MWCNTswas carried out by oxyfluorination to introduce the func-tional groups on the hydrophobic MWCNTs The elec-trical conductivity increased significantly by incorporatingthe oxyfluorinated MWCNTs and the more MWCNT con-tent gave the higher electrical conductivity The nanofibershowed the higher electrical conductivity when MWCNTswere oxyfluorinated with higher oxygen content due to theimproved dispersion of MWCNTs in the polymer matricesPVAPAAMWCNT nanofibers showed more than 80 cellviability and were tested as drug delivery device The drugrelease behavior of nanofibers showed the similar trend withthat of swelling behavior The amount of released drugwhich was related to the swelling of the system increased byincreasing the content ofMWCNTs and oxyfluorination withhigher oxygen content and by applying an external electricfield [147]

The swelling ratio of nanofibers decreasedwith increasingthe MWCNT content due to the restriction of swelling in thepresence of MWNTs The additional physical cross-linkingresulting from the favorable interaction between MWCNTsand hydrophilic polymers contributed partly to the reductionof swelling of nanofibers A totally different swelling behavioroccurred by applying electric field on the hydrogel nanofibersThe swelling ratio of nanofibers increased under electric fieldwith increasing the MWCNT content thus MWCNTs couldmake the efficient pathway of electric field due to their ownelectrical conductivity This role of MWCNTs contributed alarge share to increasing the swelling of nanofibers by accel-erating the ionization of functional groups in the hydrophilicpolymers

In a similarwork authors explored the dual-stimuli sensi-tivity of MWCNTPVAPAAc composite microcapsules pre-pared by using multiwalled carbon nanotubes (MWCNTs)poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAAc)PAAc was extensively studied as a pH-sensitive polymer andits pendant carboxylic acid groups are generally ionized into

carboxylate anions above its pKa of 47 The carboxylateanions cause more electrostatic repulsion and hydrophilicityto the polymer segments in the hydrogel Therefore as thepH increased the PVAPAAc hydrogels swelled more rapidlydue to a large swelling driving force caused by the electro-static repulsion between the ionized carboxylate groups Therelease amount of an anionic model drug such as coomassiebrilliant blue (CBB) increased in a basic buffer solution dueto the higher swelling of microcapsule shell The drug releasebehavior was closely related to the morphology of compositemicrocapsules When the MWCNTs were dispersed uni-formly in the composite microcapsule the drug was releasedmore effectively under the electric field applied and this wasattributed to the electrical networks of MWCNTs in thecomposite microcapsules which were effective to respondto the electric field The increased conductivity of compositemicrocapsule by MWCNTs could accelerate the ionization ofcarboxyl groups in polymer chains The increased degree ofionization of polyelectrolyte hydrogel under electric field wasreported to be responsible for the higher swelling ratio dueto the more electrostatic repulsion and hydrophilicity in thepolymer chains [27]

Carboxymethyl guar gum (CMG) chemically modifiedMWNT hybrid hydrogels were synthesized at differentMWNT levels as potential device for sustained transdermalrelease of diclofenac sodium The hydrogel was synthesizedby noncovalent functionalization of acid-treated CNT withcarboxymethyl guar gum Spectroscopy together with mor-phology thermogravimetry and rheological studies provedrelatively strong CMG-MWNT interaction at 05 and 1 wtlevels of MWNT whereas de-wetting was increased withhigher MWNT concentration Drug encapsulation tendencyincreased with addition of MWNT maximum entrapmentwas noticed at 1 wt MWNT level while at higher MWNTlevel the interaction level falls especially at high temperaturePresence of MWNTs enhances diclofenac sodium retentionefficiency inside the hydrogel maxima been shown at 1 wtlevel Hydrogels containing 05 1 and 3wt MWNT exhib-ited slower transdermal release than neat CMGdue to slightlyhigher gel viscosity and more drug entrapment Slowest butsteady release following non-Fickian type mechanism wasobtained from 1wtMWNT loaded hydrogel due to highest


H3C

H3C

CH3

CH3

NH2

CNTs

Gentamicin

O

O

O

O

O

O

O

O

minus

Ominus

Ominus

OH

OH

OH

HN

NH3+

NH2+

NH3+

Figure 3 Interactions of CNTs with gentamicin sulphate

viscous resistance among all other hybrid nanocomposites[8]

The sustained release effects of a hybrid hydrogel ongentamicin sulphate were significantly improvedThe releasekinetics was characterized by an initial period of rapid releaseduring the first 1 day followed by a nearly constant slowrelease rate It can be assumed that initially the unboundportion of gentamicin sulphate in thematrix diffused throughthe hydrogel After this stage desorption of matrix-boundgentamicin sulphate becomes the limiting route for the drugtransport across the hydrogel The better release effect isobtained by the CNTs hybrid hydrogel due to the many sitesof CNTs suitable for drug adsorption (Figure 3) [34]

An electrosensitive transdermal drug delivery systemwasalso prepared by the electrospinning method to control drugrelease A semi-interpenetrating polymer network was pre-pared as the matrix with polyethylene oxide (PEO) and pen-taerythritol triacrylate polymers (PETA)Multiwalled carbonnanotubes were used as an additive to increase the electri-cal sensitivity and the release experiment was carried outunder different electric voltage conditions Drug release waseffectively increased with increasing applied electric voltage

due to the excellent conductivity of the carbon additivesWater insoluble crosslinked PETA polymers form the mainstructure of the composite device and water-soluble PEO iswithin the network of PETA polymersThe drugs are trappedamong the copolymers and the resultant semi-IPN structureallows for the retarded solvation of the PEO polymer due tothe physical trapping effect of PEO in the PETA networkThe main mechanism of drug release from the copolymernetwork is by dissolving the PEO polymers Dissolution ofPEO polymers indeed creates empty spaces which formthe route for releasing the drug The polymer weight losswas assessed and was found to increase significantly withincreasing applied electric voltage This was related to thefact that solvation of PEO might be accelerated due to themore rapidmovement of ions and the swelled PETApolymerswhen high electric voltage is applied to the whole system[148]

The preparation of an electroresponsive multiwalled car-bon nanotubepoly(methylacrylic acid) (MWNTPMAA)-based hybrid material is reported in a recent work [149]The importance of this study is that for the first timeit was possible to carry out in vivo experiments to prove


NH2

SO3H

SO3H

SO3Na

SO3Na

SO3Na SO3Na

H2N

minus

minus

+

+

minus

+

minus

+

ONO

80∘ 20 h

n

Figure 4 Schematic illustrations of functionalization of carbon nanotubes by amyloid fibrils

the possibility to achieve a controlled drug release uponthe ONOFF application of an electric field giving pulsatilerelease profiles

Particular kinds of hybrid hydrogels are those based onamyloid fibrils [150] and DNA [151]

Biocompatible pH-responsive and fully fibrous hydro-gels have been prepared based on amyloid fibrils hybridizedand gelled by functionalized MWNTs far below the gellingconcentration of amyloid fibrils The sulfonic functionalgroups were introduced on the surfaces of MWNTs either by


a covalent pathway using a mild and environmental friendlydiazonium reaction or by a physical procedure via pyrenesulfonic acid capable of bindingMWNTs via120587-120587 interactions(Figure 4) The resulting hydrogels exhibit reversible pH-response gelling at acidic pH lower that the pI of the amyloidfibrils and flowing at pH gt pI Individual MWNTs canbind several amyloid fibrils at different positions leading tomultiple physical interaction points This clearly indicatesthat MWNTs can act as efficient cross-linkers in a dispersionof amyloid fibrils Indeed at higher concentrations and atpH 2 the amyloid fibrils did complex with MWNTs leadingto an interconnected network in water Since many proteinscan form amyloid fibrils with various properties this studyprovides the potential to prepare responsive hydrogels ondemand which could serve in biological applications drugrelease sensors and tissue engineering [150]

DNA hydrogels formed entirely by unconstrainedbranched DNA nanostructures are emerging as promisingmaterials for biomedical application DNA has beenindeed proved as ideal molecules in constructingprecisely controllable two- and three-dimensional DNAnanostructures In a recent work authors report on thepreparation of a DNA-single walled carbon nanotube(SWNT) hybrid hydrogel which is pH-responsive andstrength tunable The DNA-SWNT hybrid hydrogel consistsof two components the linear unit is a 12 bp long duplexwith a sticky domain at each end and the cross-linking unitis SWNT wrapped by specially designed DNA structureswhich can leave multiple sticky domains sticking out Thishydrogel is able to change into sol state within one minute atpH 80 [151]

Finally the possibility to obtain interesting hydrogels byusing CNTs alone and nanotube-graphene hybrid hydrogelsshould be cited

Hydrogels based on CNTs were prepared by oxidizingingle-walled carbon nanotubes by a technique previouslydeveloped for the oxidation of graphite to graphite oxideThis process involves treatment with concentrated H

2SO4

containing (NH4)2S2O8and P

2O5 followed by H

2SO4and

KMnO4 Oxidation results in complete exfoliation of nan-

otube ropes to yield individual oxidized tubes that are 40ndash500 nm long The oxidized nanotubes slowly form viscoushydrogels at unusually low concentration (03 wt ) and thisbehavior is attributed to the formation of a hydrogen-bondednanotube networkThe oxidized tubes bind readily to amine-coated surfaces on which they adsorb as smooth and densemonolayer films Thin films of the oxidized nanotubes showohmic current-voltage behavior with resistivities in the rangeof 02ndash05Ohm-cm [152]

Another research study focused on the preparation ofcarbon nanotube-graphene hybrid aerogels by supercriticalCO2drying of the hydrogel precursors obtained from heat-

ing the aqueous mixtures of graphene oxide and carbonnanotubes with vitamin C without stirring The resultinghybrid aerogels showed very promising performance in waterpurification including capacitive deionization of light metalsalts removal of organic dyes and enrichment of heavymetal ions Assembling graphene and CNT hybrid aerogelswhich may integrate the intriguing properties of graphene

sheets and CNTs and unique characteristics of aerogelswould create new bulk materials with desired structures andcharming properties [153]

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

Financial support of Regional Operative Program (ROP)Calabria ESF 20072013-IV Axis Human Capital-OperativeObjective M2-Action D5 is gratefully acknowledged

References

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[2] G Cirillo F Iemma F Puoci et al ldquoImprinted hydrophilicnanospheres as drug delivery systems for 5-fluorouracil sus-tained releaserdquo Journal of Drug Targeting vol 17 no 1 pp 72ndash772009

[3] N S Satarkar D Biswal and J Z Hilt ldquoHydrogel nanocompos-ites a review of applications as remote controlled biomaterialsrdquoSoft Matter vol 6 no 11 pp 2364ndash2371 2010

[4] K J Morrow Jr R Bawa and CWei ldquoRecent advances in basicand clinical nanomedicinerdquo Medical Clinics of North Americavol 91 no 5 pp 805ndash843 2007

[5] A C A Wan and J Y Ying ldquoNanomaterials for in situcell delivery and tissue regenerationrdquo Advanced Drug DeliveryReviews vol 62 no 7-8 pp 731ndash740 2010

[6] L Yang X Zhang M Ye et al ldquoAptamer-conjugated nanoma-terials and their applicationsrdquoAdvanced Drug Delivery Reviewsvol 63 no 14-15 pp 1361ndash1370 2011

[7] N Daum C Tscheka A Neumeyer and M Schneider ldquoNovelapproaches for drug delivery systems in nanomedicine effectsof particle design and shaperdquo Wiley Interdisciplinary ReviewsNanomedicine and Nanobiotechnology vol 4 no 1 pp 52ndash652012

[8] A Giri M Bhowmick S Pal and A Bandyopadhyay ldquoPolymerhydrogel from carboxymethyl guar gum and carbon nanotubefor sustained trans-dermal release of diclofenac sodiumrdquo Inter-national Journal of Biological Macromolecules vol 49 no 5 pp885ndash893 2011

[9] B Singh and L Pal ldquoDevelopment of sterculia gum basedwound dressings for use in drug deliveryrdquo European PolymerJournal vol 44 no 10 pp 3222ndash3230 2008

[10] L Sorbara L Jones and D Williams-Lyn ldquoContact lensinduced papillary conjunctivitis with silicone hydrogel lensesrdquoContact Lens and Anterior Eye vol 32 no 2 pp 93ndash96 2009

[11] J Wu W Wei L-Y Wang Z-G Su and G-H Ma ldquoAthermosensitive hydrogel based on quaternized chitosan andpoly(ethylene glycol) for nasal drug delivery systemrdquo Biomate-rials vol 28 no 13 pp 2220ndash2232 2007

[12] Y Samchenko Z Ulberg and O Korotych ldquoMultipurposesmart hydrogel systemsrdquo Advances in Colloid and InterfaceScience vol 168 no 1-2 pp 247ndash262 2011


[13] J Kost and R Langer ldquoResponsive polymeric delivery systemsrdquoAdvanced Drug Delivery Reviews vol 46 no 1ndash3 pp 125ndash1482001

[14] L Zhang J Zhao J Zhu C He and H Wang ldquoAnisotropictough poly(vinyl alcohol) hydrogelsrdquo Soft Matter vol 8 no 40pp 10439ndash10447 2012

[15] H He L Li and L J Lee ldquoPhotopolymerization and structureformation ofmethacrylic acid based hydrogels the effect of lightintensityrdquo Reactive and Functional Polymers vol 68 no 1 pp103ndash113 2008

[16] A Zhu Z Shi J Jin G Li and J Jiang ldquoSynthesis and prop-erties of polyacrylamide-based conducting gels with enhancedmechanical strengthrdquo Journal of Macromolecular Science B vol51 no 11 pp 2183ndash2190 2012

[17] S Samanta S Das R Layek D Chatterjee and A NandildquoPolythiophene-g-poly(dimethylaminoethyl methacrylate)doped methyl cellulose hydrogel behaving like a polymericAND logic gaterdquo Soft Matter vol 8 no 22 pp 6066ndash60722012

[18] P Li X Dou Y Tang et al ldquoGelator-polysaccharide hybridhydrogel for selective and controllable dye releaserdquo Journal ofColloid and Interface Science vol 387 no 1 pp 115ndash122 2012

[19] D Della Rocca B Willenberg L Ferreira et al ldquoA degrad-able bioactive gelatinized alginate hydrogel to improve stemcellgrowth factor delivery and facilitate healing after myocar-dial infarctionrdquoMedical Hypotheses vol 79 no 5 pp 673ndash6772012

[20] D T Bobokalonov Z K Mukhidinov I F Rakhimov FM Khodzhaeva G F Kasymova and L S Liu ldquoPiroxicamex vivo release kinetics from zeinpectin delivery systemsrdquoPharmaceutical Chemistry Journal vol 46 no 6 pp 378ndash3802012

[21] A Bernkop-Schnurch and S Dunnhaupt ldquoChitosan-baseddrug delivery systemsrdquo European Journal of Pharmaceutics andBiopharmaceutics vol 81 no 3 pp 463ndash469 2012

[22] L-M Zhang C-X Wu J-Y Huang X-H Peng P Chen andS-Q Tang ldquoSynthesis and characterization of a degradablecomposite agaroseHA hydrogelrdquo Carbohydrate Polymers vol88 no 4 pp 1445ndash1452 2012

[23] A S Hoffman ldquoHydrogels for biomedical applicationsrdquoAdvanced Drug Delivery Reviews vol 54 no 1 pp 3ndash12 2002

[24] S J Kim S G Yoon Y M Lee and S I Kim ldquoElectricalsensitive behavior of poly(vinyl alcohol)poly (diallyldimethy-lammonium chloride) IPN hydrogelrdquo Sensors and Actuators Bvol 88 no 3 pp 286ndash291 2003

[25] H Li Z Yuan K Y Lam et al ldquoModel development andnumerical simulation of electric-stimulus-responsive hydrogelssubject to an externally applied electric fieldrdquo Biosensors andBioelectronics vol 19 no 9 pp 1097ndash1107 2004

[26] Q Meng and J Hu ldquoA review of shape memory polymercomposites and blendsrdquo Composites Part A vol 40 no 11 pp1661ndash1672 2009

[27] J Yun J S Im Y-S Lee T-S Bae Y-M Lim and H-IKim ldquoPH and electro-responsive release behavior of MWCNTPVAPAAc composite microcapsulesrdquo Colloids and Surfaces Avol 368 no 1ndash3 pp 23ndash30 2010

[28] W Zhang Z Zhang and Y Zhang ldquoThe application of carbonnanotubes in target drug delivery systems for cancer therapiesrdquoNanoscale Research Letters vol 6 article 555 pp 1ndash22 2011

[29] G Cirillo S Hampel R Klingeler et al ldquoAntioxidant multi-walled carbon nanotubes by free radical grafting of gallic acid

newmaterials for biomedical applicationsrdquo Journal of Pharmacyand Pharmacology vol 63 no 2 pp 179ndash188 2011

[30] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines I pharmaceutical propertiesrdquoNanomedicine Nanotechnology Biology and Medicine vol 4no 3 pp 173ndash182 2008

[31] K Donaldson R Aitken L Tran et al ldquoCarbon nanotubes areview of their properties in relation to pulmonary toxicologyand workplace safetyrdquo Toxicological Sciences vol 92 no 1 pp5ndash22 2006

[32] A Peigney C Laurent E Flahaut R R Bacsa and A RoussetldquoSpecific surface area of carbon nanotubes and bundles ofcarbon nanotubesrdquo Carbon vol 39 no 4 pp 507ndash514 2001

[33] A Taylor K Lipert K Kramer et al ldquoBiocompatibility of ironfilled carbon nanotubes in vitrordquo Journal of Nanoscience andNanotechnology vol 9 no 10 pp 5709ndash5716 2009

[34] H Li J He Y Zhao G Wang and Q Wei ldquoThe effect ofcarbon nanotubes added into bullfrog collagen hydrogel ongentamicin sulphate release in vitrordquo Journal of Inorganic andOrganometallic Polymers and Materials vol 21 no 4 pp 890ndash892 2011

[35] H Li D Q Wang B L Liu and L Z Gao ldquoSynthesis of anovel gelatin-carbon nanotubes hybrid hydrogelrdquo Colloids andSurfaces B vol 33 no 2 pp 85ndash88 2004

[36] B F Erlanger B-X Chen M Zhu and L Brus ldquoBinding ofan anti-fullerene iggmonoclonal antibody to single wall carbonnanotubesrdquo Nano Letters vol 1 no 9 pp 465ndash467 2001

[37] F Balavoine P Schultz C Richard V Mallouh T W Ebbesenand C Mioskowski ldquoHelical crystallization of proteins oncarbon nanotubes a first step towards the development of newbiosensorsrdquo Angewandte Chemie vol 38 no 13-14 pp 1912ndash1915 1999

[38] M P Mattson R C Haddon and A M Rao ldquoMolecularfunctionalization of carbon nanotubes and use as substrates forneuronal growthrdquo Journal ofMolecular Neuroscience vol 14 no3 pp 175ndash182 2000

[39] Z Guo P J Sadler and S C Tsang ldquoImmobilization andvisualization of DNA and proteins on carbon nanotubesrdquoAdvanced Materials vol 10 no 9 pp 701ndash703 1998

[40] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocom-patibility issuesrdquo Nanomedicine Nanotechnology Biology andMedicine vol 4 no 3 pp 183ndash200 2008

[41] Y Zhang Y Bai and B Yan ldquoFunctionalized carbon nanotubesfor potentialmedicinal applicationsrdquoDrugDiscovery Today vol15 no 11-12 pp 428ndash435 2010

[42] CKlumppKKostarelosM Prato andA Bianco ldquoFunctional-ized carbon nanotubes as emerging nanovectors for the deliveryof therapeuticsrdquo Biochimica et Biophysica Acta vol 1758 no 3pp 404ndash412 2006

[43] A Bianco K Kostarelos and M Prato ldquoApplications of carbonnanotubes in drug deliveryrdquo Current Opinion in ChemicalBiology vol 9 no 6 pp 674ndash679 2005

[44] G Pastorin ldquoCrucial functionalizations of carbon nanotubesfor improved drug delivery a valuable optionrdquo PharmaceuticalResearch vol 26 no 4 pp 746ndash769 2009

[45] Z Liu X Sun N Nakayama-Ratchford and H Dai ldquoSupramo-lecular chemistry on water- Soluble carbon nanotubes for drugloading and deliveryrdquo ACS Nano vol 1 no 1 pp 50ndash56 2007

[46] H Maeda G Y Bharate and J Daruwalla ldquoPolymeric drugsfor efficient tumor-targeted drug delivery based on EPR-effectrdquo


European Journal of Pharmaceutics and Biopharmaceutics vol71 no 3 pp 409ndash419 2009

[47] N W S Kam and H Dai ldquoCarbon nanotubes as intracellularprotein transporters generality and biological functionalityrdquoJournal of the American Chemical Society vol 127 no 16 pp6021ndash6026 2005

[48] N W S Kam Z Liu and H Dai ldquoCarbon nanotubes as intra-cellular transporters for proteins and DNA an investigation ofthe uptake mechanism and pathwayrdquo Angewandte Chemie vol45 no 4 pp 577ndash581 2006

[49] D Pantarotto C D Partidos R Graff et al ldquoSynthesisstructural characterization and immunological properties ofcarbon nanotubes functionalized with peptidesrdquo Journal of theAmericanChemical Society vol 125 no 20 pp 6160ndash6164 2003

[50] A E PorterM Gass KMuller J N Skepper P AMidgley andMWelland ldquoDirect imaging of single-walled carbon nanotubesin cellsrdquoNature Nanotechnology vol 2 no 11 pp 713ndash717 2007

[51] A Bianco K Kostarelos and M Prato ldquoMaking carbonnanotubes biocompatible and biodegradablerdquo Chemical Com-munications vol 47 no 37 pp 10182ndash10188 2011

[52] A D Gilmour R A Green and C E Thomson ldquoA low-maintenance primary cell culture model for the assessmentof carbon nanotube toxicityrdquo Toxicological amp EnvironmentalChemistry 2013

[53] A Helland P Wick A Koehler K Schmid and C SomldquoReviewing the environmental and human health knowledgebase of carbon nanotubesrdquo Environmental Health Perspectivesvol 115 no 8 pp 1125ndash1131 2007

[54] B N Snyder-Talkington Y Qian V Castranova and N LGuo ldquoNew perspectives in vitro risk assessment of multiwalledcarbon nanotubes application of coculture and bioinformaticsrdquoJournal of Toxicology and Environmental Health B vol 15 pp468ndash492 2012

[55] G Oberdorster E Oberdorster and J Oberdorster ldquoNan-otoxicology an emerging discipline evolving from studies ofultrafine particlesrdquo Environmental Health Perspectives vol 113no 7 pp 823ndash839 2005

[56] X Shi B Sitharaman Q P Pham et al ldquoIn vitro cytotoxic-ity of single-walled carbon nanotubebiodegradable polymernanocompositesrdquo Journal of Biomedical Materials Research Avol 86 no 3 pp 813ndash823 2008

[57] PNewmanAMinett R Ellis-Behnke andH Zreiqat ldquoCarbonnanotubes their potential and pitfalls for bone tissue regenera-tion and engineeringrdquoNanomedicine vol 9 no 8 pp 1139ndash11582013

[58] B Sitharaman X Shi X F Walboomers et al ldquoIn vivobiocompatibility of ultra-short single-walled carbon nanotubebiodegradable polymer nanocomposites for bone tissue engi-neeringrdquo Bone vol 43 no 2 pp 362ndash370 2008

[59] C-W Lam J T James R McCluskey and R L HunterldquoPulmonary toxicity of single-wall carbon nanotubes in mice7 and 90 days after intractracheal instillationrdquo ToxicologicalSciences vol 77 no 1 pp 126ndash134 2004

[60] S Kang M Herzberg D F Rodrigues and M ElimelechldquoAntibacterial effects of carbon nanotubes size does matterrdquoLangmuir vol 24 no 13 pp 6409ndash6413 2008

[61] D B Warheit ldquoWhat is currently known about the health risksrelated to carbon nanotube exposuresrdquo Carbon vol 44 no 6pp 1064ndash1069 2006

[62] C A Poland R Duffin I Kinloch et al ldquoCarbon nanotubesintroduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot studyrdquo Nature Nanotechnology vol3 no 7 pp 423ndash428 2008

[63] H Dumortier ldquoWhen carbon nanotubes encounter theimmune system desirable and undesirable effectsrdquo AdvancedDrug Delivery Reviews vol 65 no 15 pp 2120ndash2126 2013

[64] M T Byrne and Y K GuinrsquoKo ldquoRecent advances in research oncarbon nanotubemdashpolymer compositesrdquo Advanced Materialsvol 22 no 15 pp 1672ndash1688 2010

[65] D Pantarotto C D Partidos J Hoebeke et al ldquoImmunizationwith peptide-functionalized carbon nanotubes enhances virus-specific neutralizing antibody responsesrdquo Chemistry and Biol-ogy vol 10 no 10 pp 961ndash966 2003

[66] R Singh D Pantarotto L Lacerda et al ldquoTissue biodistributionand blood clearance rates of intravenously administered carbonnanotube radiotracersrdquo Proceedings of the National Academy ofSciences of the United States of America vol 103 no 9 pp 3357ndash3362 2006

[67] K Yang J Wan S Zhang Y Zhang S-T Lee and Z Liu ldquoInvivo pharmacokinetics long-term biodistribution and toxicol-ogy of pegylated graphene in micerdquo ACS Nano vol 5 no 1 pp516ndash522 2011

[68] K Von Der Mark J Park S Bauer and P Schmuki ldquoNanoscaleengineering of biomimetic surfaces cues from the extracellularmatrixrdquo Cell and Tissue Research vol 339 no 1 pp 131ndash1532010

[69] B L Allen P D Kichambare P Gou et al ldquoBiodegradation ofsingle-walled carbon nanotubes through enzymatic catalysisrdquoNano Letters vol 8 no 11 pp 3899ndash3903 2008

[70] J Russier C Menard-Moyon E Venturelli et al ldquoOxidativebiodegradation of single- and multi-walled carbon nanotubesrdquoNanoscale vol 3 no 3 pp 893ndash896 2011

[71] G P Kotchey Y Zhao V E Kagan and A Star ldquoPeroxidase-mediated biodegradation of carbon nanotubes in vitro and invivordquo Advanced Drug Delivery Reviews vol 65 no 15 pp 1921ndash1932 2013

[72] V E Kagan N V Konduru W Feng et al ldquoCarbon nan-otubes degraded by neutrophil myeloperoxidase induce lesspulmonary inflammationrdquo Nature Nanotechnology vol 5 no5 pp 354ndash359 2010

[73] G Cirillo F Iemma U G Spizzirri et al ldquoSynthesis of stimuli-responsive microgels for in vitro release of diclofenac diethylammoniumrdquo Journal of Biomaterials Science Polymer Editionvol 22 no 4ndash6 pp 823ndash844 2011

[74] I Altimari U G Spizzirri F Iemma M Curcio F Puoci andN Picci ldquopH-sensitive drug delivery systems by radical poly-merization of gelatin derivativesrdquo Journal of Applied PolymerScience vol 125 no 4 pp 3006ndash3013 2012

[75] H Li D QWang H L Chen B L Liu and L Z Gao ldquoA novelgelatin-carbon nanotubes hybrid hydrogelrdquo MacromolecularBioscience vol 3 no 12 pp 720ndash724 2003

[76] D J A Crommelin K Park and A Florence ldquoPharmaceuticalnanotechnology unmet needs in drug deliveryrdquo Journal ofControlled Release vol 141 no 3 pp 263ndash264 2010

[77] N S Satarkar D Johnson B Marrs et al ldquoHydrogel-MWCNTnanocomposites synthesis characterization and heating withradiofrequency fieldsrdquo Journal of Applied Polymer Science vol117 no 3 pp 1813ndash1819 2010

[78] P Schexnailder and G Schmidt ldquoNanocomposite polymerhydrogelsrdquo Colloid and Polymer Science vol 287 no 1 pp 1ndash112009


[79] A J Lovinger ldquoNano- bio- multi- inter- polymer researchin an era of prefixesrdquo Journal of Macromolecular Science vol 45no 3 pp 195ndash199 2005

[80] W A De Heer W S Bacsa A Chatelain et al ldquoAlignedcarbon nanotube films production and optical and electronicpropertiesrdquo Science vol 268 no 5212 pp 845ndash847 1995

[81] S J Park S T Lim M S Cho H M Kim J Joo andH J Choi ldquoElectrical properties of multi-walled carbonnanotubepoly(methyl methacrylate) nanocompositerdquo CurrentApplied Physics vol 5 no 4 pp 302ndash304 2005

[82] D K Aktas G A Evingur and O Pekcan ldquoCritical exponentsof gelation and conductivity in polyacrylamide gels doped bymultiwalled carbon nanotubesrdquoComposite Interfaces vol 17 no4 pp 301ndash318 2010

[83] F Hua Y Sun A Gaur et al ldquoPolymer imprint lithographywith molecular-scale resolutionrdquoNano Letters vol 4 no 12 pp2467ndash2471 2004

[84] C Wang Z-X Guo S Fu W Wu and D Zhu ldquoPolymerscontaining fullerene or carbon nanotube structuresrdquo Progress inPolymer Science vol 29 no 11 pp 1079ndash1141 2004

[85] I-C LiuH-MHuang C-Y ChangH-C Tsai C-HHsu andR C-C Tsiang ldquoPreparing a styrenic polymer composite con-taining well-dispersed carbon nanotubes anionic polymeriza-tion of a nanotube-bound p-methylstyrenerdquo Macromoleculesvol 37 no 2 pp 283ndash287 2004

[86] D Baskaran J W Mays and M S Bratcher ldquoPolymer-graftedmultiwalled carbon nanotubes through surface-initiated poly-merizationrdquo Angewandte Chemie vol 43 no 16 pp 2138ndash21422004

[87] D Yan and G Yang ldquoA novel approach of in situ graftingpolyamide 6 to the surface of multi-walled carbon nanotubesrdquoMaterials Letters vol 63 no 2 pp 298ndash300 2009

[88] K Mylvaganam and L C Zhang ldquoNanotube functionalizationand polymer grafting an ab initio studyrdquo Journal of PhysicalChemistry B vol 108 no 39 pp 15009ndash15012 2004

[89] C Gao S Muthukrishnan W Li J Yuan Y Xu andA H E Muller ldquoLinear and hyperbranched glycopolymer-functionalized carbon nanotubes synthesis kinetics and char-acterizationrdquoMacromolecules vol 40 no 6 pp 1803ndash1815 2007

[90] H Li F Cheng A M Duft and A Adronov ldquoFunctional-ization of single-walled carbon nanotubes with well-definedpolystyrene by ldquoclickrdquo couplingrdquo Journal of the American Chem-ical Society vol 127 no 41 pp 14518ndash14524 2005

[91] H Kong P Luo C Gao and D Yan ldquoPolyelectrolyte-functionalized multiwalled carbon nanotubes preparationcharacterization and layer-by-layer self-assemblyrdquo Polymer vol46 no 8 pp 2472ndash2485 2005

[92] R B Martin L Qu Y Lin et al ldquoFunctionalized carbonnanotubes with tethered pyrenes synthesis and photophysicalpropertiesrdquo Journal of Physical Chemistry B vol 108 no 31 pp11447ndash11453 2004

[93] F J Gomez R J Chen D Wang R M Waymouth andH Dai ldquoRing opening metathesis polymerization on non-covalently functionalized single-walled carbon nanotubesrdquoChemical Communications vol 9 no 2 pp 190ndash191 2003

[94] G Cirillo T Caruso S Hampel et al ldquoNovel carbon nanotubecomposites by grafting reaction with water-compatible redoxinitiator systemrdquo Colloid and Polymer Science vol 291 no 3pp 699ndash708 2013

[95] X Lou C Detrembleur C Pagnoulle et al ldquoSurface modifica-tion of multiwalled carbon nanotubes by poly(2-vinylpyridine)

dispersion selective deposition and decoration of the nan-otubesrdquo Advanced Materials vol 16 no 23-24 pp 2123ndash21272004

[96] H-M Huang I-C Liu C-Y U Chang H-C Tsai C-H Hsuand R C-C Tsiang ldquoPreparing a polystyrene-functionalizedmultiple-walled carbon nanotubes via covalently linking acylchloride functionalities with living polystyryllithiumrdquo Journalof Polymer Science A vol 42 no 22 pp 5802ndash5810 2004

[97] S Qin D Qin W T Ford J E Herrera and D E ResascoldquoGrafting of poly(4-vinylpyridine) to single-walled carbon nan-otubes and assembly of multilayer filmsrdquo Macromolecules vol37 no 26 pp 9963ndash9967 2004

[98] X Dai Z Liu B Han et al ldquoCarbon nanotubepoly(24-hexadiyne-16-diol) nanocomposites prepared with the aid ofsupercritical CO2rdquo Chemical Communications vol 10 no 19pp 2190ndash2191 2004

[99] H Xu X Wang Y Zhang and S Liu ldquoSingle-step in situpreparation of polymer-grafted multi-walled carbon nanotubecomposites under60Co 120574-ray irradiationrdquo Chemistry of Materi-als vol 18 no 13 pp 2929ndash2934 2006

[100] P Petrov X Lou C Pagnoulle C Jerome C Calberg and RJerome ldquoFunctionalization of multi-walled carbon nanotubesby electrografting of polyacrylonitrilerdquo Macromolecular RapidCommunications vol 25 no 10 pp 987ndash990 2004

[101] H Zeng C Gao Y Wang et al ldquoIn situ polymerizationapproach to multiwalled carbon nanotubes-reinforced nylon1010 composites mechanical properties and crystallizationbehaviorrdquo Polymer vol 47 no 1 pp 113ndash122 2006

[102] A Nogales G Broza Z Roslaniec et al ldquoLow percolationthreshold in nanocomposites based on oxidized single wallcarbon nanotubes and poly(butylene terephthalate)rdquo Macro-molecules vol 37 no 20 pp 7669ndash7672 2004

[103] G XuW-TWu YWang et al ldquoSynthesis and characterizationof water-soluble multiwalled carbon nanotubes grafted by athermoresponsive polymerrdquo Nanotechnology vol 17 no 10 pp2458ndash2465 2006

[104] J CuiWWang Y You C Liu and PWang ldquoFunctionalizationof multiwalled carbon nanotubes by reversible addition frag-mentation chain-transfer polymerizationrdquo Polymer vol 45 no26 pp 8717ndash8721 2004

[105] S Chen D Chen and GWu ldquoGrafting of poly(tBA) and PtBA-b-PMMA onto the surface of SWNTs using carbanions as theinitiatorrdquo Macromolecular Rapid Communications vol 27 no11 pp 882ndash887 2006

[106] L Qu L M Veca Y Lin et al ldquoSoluble nylon-functionalizedcarbon nanotubes from anionic ring-opening polymerizationfrom nanotube surfacerdquo Macromolecules vol 38 no 24 pp10328ndash10331 2005

[107] F Buffa H Hu and D E Resasco ldquoSide-wall functionalizationof single-walled carbon nanotubes with 4-hydroxymethylani-line followed by polymerization of 120576-caprolactonerdquo Macro-molecules vol 38 no 20 pp 8258ndash8263 2005

[108] H Kong C Gao and D Yan ldquoControlled functionalization ofmultiwalled carbon nanotubes by in situ atom transfer radicalpolymerizationrdquo Journal of the American Chemical Society vol126 no 2 pp 412ndash413 2004

[109] Z Yao N Braidy G A Botton and A Adronov ldquoPolymer-ization from the surface of single-walled carbon nanotubesmdashpreparation and characterization of nanocompositesrdquo Journal ofthe American Chemical Society vol 125 no 51 pp 16015ndash160242003


[110] S Prakash M Malhotra W Shao C Tomaro-Duchesneauand S Abbasi ldquoPolymeric nanohybrids and functionalizedcarbon nanotubes as drug delivery carriers for cancer therapyrdquoAdvanced Drug Delivery Reviews vol 63 no 14-15 pp 1340ndash1351 2011

[111] X Shi B Sitharaman Q P Pham et al ldquoFabrication of porousultra-short single-walled carbonnanotube nanocomposite scaf-folds for bone tissue engineeringrdquo Biomaterials vol 28 no 28pp 4078ndash4090 2007

[112] B C Thompson S E Moulton K J Gilmore M J HigginsP G Whitten and G G Wallace ldquoCarbon nanotube biogelsrdquoCarbon vol 47 no 5 pp 1282ndash1291 2009

[113] Y S Song ldquoA passive microfluidic valve fabricated from ahydrogel filled with carbon nanotubesrdquo Carbon vol 50 no 3pp 1417ndash1421 2012

[114] V Lovat D Pantarotto L Lagostena et al ldquoCarbon nanotubesubstrates boost neuronal electrical signalingrdquo Nano Lettersvol 5 no 6 pp 1107ndash1110 2005

[115] P R Supronowicz P M Ajayan K R Ullmann B P Arulanan-dam D W Metzger and R Bizios ldquoNovel current-conductingcomposite substrates for exposing osteoblasts to alternatingcurrent stimulationrdquo Journal of Biomedical Materials Researchvol 59 no 3 pp 499ndash506 2002

[116] P Galvan-Garcia E W Keefer F Yang et al ldquoRobust cellmigration and neuronal growth on pristine carbon nanotubesheets and yarnsrdquo Journal of Biomaterials Science PolymerEdition vol 18 no 10 pp 1245ndash1261 2007

[117] A Abarrategi M C Gutierrez C Moreno-Vicente et alldquoMultiwall carbon nanotube scaffolds for tissue engineeringpurposesrdquo Biomaterials vol 29 no 1 pp 94ndash102 2008

[118] X Zhang L Meng and Q Lu ldquoCell behaviors onpolysaccharide-wrapped single-wall carbon nanotubes aquantitative study of the surface properties of biomimeticnanofibrous scaffoldsrdquo ACS Nano vol 3 no 10 pp 3200ndash32062009

[119] B Zhao HHu S KMandal and R C Haddon ldquoA bonemimicbased on the self-assembly of hydroxyapatite on chemicallyfunctionalized single-walled carbon nanotubesrdquo Chemistry ofMaterials vol 17 no 12 pp 3235ndash3241 2005

[120] L P Zanello B Zhao H Hu and R C Haddon ldquoBone cellproliferation on carbon nanotubesrdquo Nano Letters vol 6 no 3pp 562ndash567 2006

[121] S Chatterjee MW Lee and S HWoo ldquoEnhancedmechanicalstrength of chitosan hydrogel beads by impregnation withcarbon nanotubesrdquo Carbon vol 47 no 12 pp 2933ndash2936 2009

[122] C J Ferris and M In Het Panhuis ldquoConducting bio-materialsbased on gellan gum hydrogelsrdquo Soft Matter vol 5 no 18 pp3430ndash3437 2009

[123] F Puoci S Hampel O I Parisi A Hassan G Cirillo and NPicci ldquoI mprinted microspheres doped with carbon nanotubesas novel electroresponsive drug-delivery systemsrdquo Journal ofApplied Polymer Science vol 130 no 2 pp 829ndash834 2013

[124] G Cirillo O Vittorio S Hampel et al ldquoQuercetin nanocom-posite as novel anticancer therapeutic improved efficinencyand reduced toxicityrdquo European Journal of PharmaceuticalSciences vol 49 no 3 pp 359ndash365 2013

[125] A A Rodrigues N A Batista V P Bavaresco et al ldquoIn vivoevaluation of hydrogels of polyvinyl alcohol with and withoutcarbon nanoparticles for osteochondral repairrdquo Carbon vol 50no 6 pp 2091ndash2099 2012

[126] Y Huang Y Zheng W Song Y Ma J Wu and L FanldquoPoly(vinyl pyrrolidone) wrapped multi-walled carbon nan-otubepoly(vinyl alcohol) composite hydrogelsrdquo CompositesPart A vol 42 no 10 pp 1398ndash1405 2011

[127] X Shen L Chen X Cai T Tong H Tong and J Hu ldquoAnovel method for the fabrication of homogeneous hydroxyap-atitecollagen nanocomposite and nanocomposite scaffold withhierarchical porosityrdquo Journal of Materials Science vol 22 no2 pp 299ndash305 2011

[128] P Calvo-Marzal M Delaney J Auletta et al ldquoManipulatingmechanical properties with electricity electroplastic elastomerhydrogelsrdquo ACS Macro Letters vol 1 no 1 pp 204ndash208 2012

[129] S H Hong T T Tung L K H Trang T Y Kim and K SSuh ldquoPreparation of single-walled carbon nanotube (SWNT)gel composites using poly(ionic liquids)rdquo Colloid and PolymerScience vol 288 no 9 pp 1013ndash1018 2010

[130] X Zhang J Liu B Xu Y Su and Y Luo ldquoUltralight conductingpolymercarbon nanotube composite aerogelsrdquoCarbon vol 49no 6 pp 1884ndash1893 2011

[131] K-S Kim and S-J Park ldquoInfluence of dispersion of multi-walled carbon nanotubes on the electrochemical performanceof PEDOT-PSS filmsrdquoMaterials Science and Engineering B vol176 no 3 pp 204ndash209 2011

[132] Y Xiao L He and J Che ldquoAn effective approach for thefabrication of reinforced composite hydrogel engineered withSWNTs polypyrrole and PEGDA hydrogelrdquo Journal of Materi-als Chemistry vol 22 no 16 pp 8076ndash8082 2012

[133] V Saez-Martinez A Garcia-Gallastegui C Vera et al ldquoNewhybrid system poly(ethylene glycol) hydrogel with covalentlybonded pegylated nanotubesrdquo Journal of Applied Polymer Sci-ence vol 120 no 1 pp 124ndash132 2011

[134] Y Ye Y Mao H Wang and Z Ren ldquoHybrid structureof pH-responsive hydrogel and carbon nanotube array withsuperwettabilityrdquo Journal of Materials Chemistry vol 22 no 6pp 2449ndash2455 2012

[135] T Ogoshi Y Takashima H Yamaguchi and A HaradaldquoChemically-responsive sol-gel transition of supramolecularsingle-walled carbon nanotubes (SWNTs) hydrogel made byhybrids of SWNTs and cyclodextrinsrdquo Journal of the AmericanChemical Society vol 129 no 16 pp 4878ndash4879 2007

[136] K Sui S Gao W Wu and Y Xia ldquoInjectable supramolecularhybrid hydrogels formed by MWNT-grafted- poly(ethyleneglycol) and 120572-cyclodextrinrdquo Journal of Polymer Science A vol48 no 14 pp 3145ndash3151 2010

[137] Z Hui X Zhang J Yu et al ldquoCarbon nanotube-hybridizedsupramolecular hydrogel based on PEO-b-PPO-b-PEO120572-cyclodextrin as a potential biomaterialrdquo Journal of AppliedPolymer Science vol 116 no 4 pp 1894ndash1901 2010

[138] G A Evingur and O Pekcan ldquoMonitoring of dynamicalprocesses in PAAmaCrdquo MWNTs composites by fluorescencemethodrdquo Advanced Composite Materials vol 21 no 2 pp 193ndash208 2012

[139] G A Evingr and O Pekcan ldquoElastic percolation of swollenpolyacrylamide (PAAm)-multiwall carbon nanotubes compos-iterdquo Phase Transitions vol 85 no 6 pp 553ndash564 2012

[140] X Zhang C L Pint M H Lee et al ldquoOptically- and thermally-responsive programmablematerials based on carbon nanotube-hydrogel polymer compositesrdquo Nano Letters vol 11 no 8 pp3239ndash3244 2011

[141] G Cirillo K Kraemer S Fuessel et al ldquoBiological activity of agallic acid-gelatin conjugaterdquo Biomacromolecules vol 11 no 12pp 3309ndash3315 2010


[142] M Curcio F Puoci U G Spizzirri et al ldquoNegative thermo-responsive microspheres based on hydrolyzed gelatin as drugdelivery devicerdquoAAPS PharmSciTech vol 11 no 2 pp 652ndash6622010

[143] G Cirillo O Vittorio S Hampel U G Spizzirri N Picci andF Iemma ldquoIncorporation of carbon nanotubes into a gelatin-catechin conjugate innovative approach for the preparation ofanticancer materialsrdquo International Journal of Pharmaceuticsvol 446 no 1-2 pp 176ndash182 2013

[144] S Haider S-Y Park K Saeed and B L Farmer ldquoSwelling andelectroresponsive characteristics of gelatin immobilized ontomulti-walled carbon nanotubesrdquo Sensors and Actuators B vol124 no 2 pp 517ndash528 2007

[145] U G Spizzirri S Hampel G Cirillo et al ldquoSphericalgelatinCNTs hybrid microgels as electro-responsive drugdelivery systemsrdquo International Journal of Pharmaceutics vol448 no 1 pp 115ndash122 2013

[146] S Roy and A Banerjee ldquoFunctionalized single walled carbonnanotube containing amino acid based hydrogel a hybridnanomaterialrdquo RSC Advances vol 2 no 5 pp 2105ndash2111 2012

[147] J Yun J S Im Y-S Lee and H-I Kim ldquoElectro-responsivetransdermal drug delivery behavior of PVAPAAMWCNTnanofibersrdquo European Polymer Journal vol 47 no 10 pp 1893ndash1902 2011

[148] J S Im B C Bai and Y-S Lee ldquoThe effect of carbon nanotubeson drug delivery in an electro-sensitive transdermal drugdelivery systemrdquo Biomaterials vol 31 no 6 pp 1414ndash1419 2010

[149] A Servant LMethven R PWilliams andK Kostarelos ldquoElec-troresponsive polymer-carbon nanotube hydrogel hybrids forpulsatile drug delivery in vivordquo Advanced Healthcare Materialsvol 2 no 6 pp 806ndash811 2013

[150] C Li and R Mezzenga ldquoFunctionalization of multiwalledcarbon nanotubes and their pH-responsive hydrogels withamyloid fibrilsrdquo Langmuir vol 28 no 27 pp 10142ndash10146 2012

[151] E Cheng Y Li Z Yang Z Deng and D Liu ldquoDNA-SWNThybrid hydrogelrdquo Chemical Communications vol 47 no 19 pp5545ndash5547 2011

[152] N I Kovtyukhova T E Mallouk L Pan and E C DickeyldquoIndividual single-walled nanotubes and hydrogels made byoxidative exfoliation of carbon nanotube ropesrdquo Journal of theAmerican Chemical Society vol 125 no 32 pp 9761ndash9769 2003

[153] Z Sui Q Meng X Zhang R Ma and B Cao ldquoGreen synthesisof carbon nanotube-graphene hybrid aerogels and their useas versatile agents for water purificationrdquo Journal of MaterialsChemistry vol 22 no 18 pp 8767ndash8771 2012

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of


StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of



Advances in Pharmacological Sciences

Tropical MedicineJournal of


Medicinal ChemistryInternational Journal of


AddictionJournal of



BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


Autoimmune Diseases


Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of


Pharmaceutics


MEDIATORSINFLAMMATION

of


represent a class of hydrophilic and crosslinked polymericnetworks insoluble in water and characterized by the abil-ity to hold a large amount of biological fluids includingwater within the spaces available among the polymericchains The water holding capacity depends on the pres-ence of hydrophilic functionalities (amido amino carboxylhydroxyl groups etc) in polymer chains and the watercontent may vary from 10 to thousands of times of theweight of the dry polymer network [9] Moreover thesepolymeric materials present a good biocompatibility and aresuitable for applications inmedical and pharmaceutical fieldsincluding wound dressings contact lenses artificial organstissue engineering and drug delivery systems [10 11]

Hydrogels can be classified according to several parame-ters such as their natural or synthetic origin and the cross-linking nature [12]

Generally all polymeric gels are either synthetic (poly(ethylene glycol) (PEG) [13] poly (vinyl alcohol) (PVA)[14] poly (acrylic acid) (PAA) [15] polyacrylamide (PAM)[16] and poly (methyl methacrylate) (PMA) [17]) or natural(alginic acid [18] pectin [19] chitin and chitosan [20]dextran [21] agarose [22] and different derivatives of thesepolymers)

According to their cross-linking nature hydrogels canbe divided into two main classes permanent hydrogels inwhich covalent bonds between polymeric chains are formedduring the cross-linking reaction and physical hydrogels inwhich the cross-linking is due to the formation of physicalinteractions such as hydrogen bonding ionic interactionvan der Waals interactions and molecular entanglementamong the polymeric chains Hydrogels based on acrylicmonomers are included in the first class while gelatine andagar-agar hydrogels are examples of materials belonging tothe second category [23]

Some of these polymeric networks are able to exhibitphase transition and changes in their equilibrium state inresponse to external stimuli and are known as ldquostimuli-responsiverdquo or ldquosmartrdquo hydrogels [24] This kind of materialsfinds application in targeted drug delivery due to the capa-bility to respond to environmental factors including physicalchemical and biochemical stimuli Physical stimuli consistof temperature pressure light electric magnetic and soundfields while chemical or biochemical stimuli involve pHionic strength ions or specific molecular recognition events[25] Stimuli-responsive hydrogels can be classified on thebasis of the external stimuli type in thermosensitive pHsensitive and electrosensitive [26] as well as sensitive tolight pressure ionic strength and different molecules forexample enzymes and so forth [27] Different strategies havebeen developed to apply the external stimuli to the hydrogelsand the main approaches involve the use of suitable bufferedsaline (phosphate or potassium) for pH responsive materialsthe increase of the temperature by hot plate andor IRirradiation in the case thermo-responsive elements and theapplication of a voltage by appropriate inert electrodes forelectroresponsive materials In the latter case it is possible tostudy the response of the hydrogel by modulating the voltageaswell as the intensity of the current Specific example of thesematters have been treated below in this review

2 Carbon Nanotubes

Carbon nanotubes (CNTs) are huge cylindrical largemolecu-les consisting of a hexagonal arrangement of sp2 hybridizedcarbon atoms (CndashC distance is about 14 A) [28 29]

The wall of CNTs is composed of one or multiplelayers of graphene sheets thus it is possible to discriminatethesematerials in single-walled carbon nanotubes (SWCNT)formed by rolling up of a single graphene sheet and mul-tiwalled CNTs (MWCNTs) formed by rolling up of morethan one graphene sheet Both SWCNTs and MWCNTsare capped at both ends of the tubes in a hemisphericalarrangement of carbon networks called fullerenes warped upby the graphene sheet (Figure 1) The interlayer separation ofthe graphene layers of MWCNTs is approximately 034 nm inaverage each one forming an individual tube and the outerdiameter ranging from 25 to 100 nm while for SWCNTs thisvalue ranges from 06 to 24 nm SWCNTs are characterizedby a better defined wall and a smaller diameter that makethem suitable as drug carriers due to their quality controlOn the contrary MWCNTs may present defects in theirnanostructure resulting in a lack of stability that makes theirmodification easier [30]

The adopted synthetic procedure influences CNTs lengthand diameter and due to attractive van der Waals forcesSWCNTs and MWCNTs tend to pack together in ropes Theobtained bundles containmany nanotubes and are longer andwider than the original ones fromwhich they are formedThisphenomenon could be important from a toxicological pointof view [31 32]

In the past few years carbon nanotubes have foundapplications in different fields including nanoelectronics andnanocomposite due to their considerable electrical mechan-ical and chemical stability but only in the recent periodthe interest was focused on their potential application asbiomedical devices [33 34]

Several research studies indeed focuses on the use ofcarbon nanotubes in biological systems [35 36] Balavoineet al used MWNTs for helical crystallization of protein [37]Mattson et al reported on the first application of carbon nan-otube technology to neuroscience research developing newapproaches for the growth of embryonic rat-brain neuronson MWNTs [38] and Sadler and coworkers immobilizedbiological species on both SWNTs and MWNTs for potentialbiosensor and bioreactor systems [39]

The employment of CNTs as drug excipients with lowtoxicity and immunogenicity is also largely investigated [40]The ability of carbon nanotubes to release drugs was studiedin the aim to obtain innovative drug vehicles to be applied inthe field of nanomedicine [41]

Different types of therapeutic molecules have beenreported to be delivered by CNTs recording better resultsthan that obtained with conventional vehicles [42ndash44] Thehigh surface area of CNTs indeed allows us to achieve ahigh loading capacity of chemotherapy drugs [45] MoreoverCNTs loaded with drugs can extravasate in tumor tissuesover time because of the enhanced permeability and retentioneffect of solid tumors [46]


Graphene sheet

Warping

Fullerene

Rolling

Capping

SWCNT

































2-















































NaMAEBA

Initiator system

MWNT

MWNT GL-NTx

Gel

Ultrasonication









H3C

H3C

CH3

CH3

NH2

CNTs

Gentamicin

O

O

O

O

O

O

O

O

minus

Ominus

Ominus

OH

OH

OH

HN

NH3+

NH2+

NH3+








NH2

SO3H

SO3H

SO3Na

SO3Na

SO3Na SO3Na

H2N

minus

minus

+

+

minus

+

minus

+

ONO

80∘ 20 h

n










2SO4


2O5 followed by H

2SO4and








Acknowledgment


References






































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


Graphene sheet

Warping

Fullerene

Rolling

Capping

SWCNT

































2-















































NaMAEBA

Initiator system

MWNT

MWNT GL-NTx

Gel

Ultrasonication









H3C

H3C

CH3

CH3

NH2

CNTs

Gentamicin

O

O

O

O

O

O

O

O

minus

Ominus

Ominus

OH

OH

OH

HN

NH3+

NH2+

NH3+








NH2

SO3H

SO3H

SO3Na

SO3Na

SO3Na SO3Na

H2N

minus

minus

+

+

minus

+

minus

+

ONO

80∘ 20 h

n










2SO4


2O5 followed by H

2SO4and








Acknowledgment


References






































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of





















2-















































NaMAEBA

Initiator system

MWNT

MWNT GL-NTx

Gel

Ultrasonication









H3C

H3C

CH3

CH3

NH2

CNTs

Gentamicin

O

O

O

O

O

O

O

O

minus

Ominus

Ominus

OH

OH

OH

HN

NH3+

NH2+

NH3+








NH2

SO3H

SO3H

SO3Na

SO3Na

SO3Na SO3Na

H2N

minus

minus

+

+

minus

+

minus

+

ONO

80∘ 20 h

n










2SO4


2O5 followed by H

2SO4and








Acknowledgment


References






































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of





2-















































NaMAEBA

Initiator system

MWNT

MWNT GL-NTx

Gel

Ultrasonication









H3C

H3C

CH3

CH3

NH2

CNTs

Gentamicin

O

O

O

O

O

O

O

O

minus

Ominus

Ominus

OH

OH

OH

HN

NH3+

NH2+

NH3+








NH2

SO3H

SO3H

SO3Na

SO3Na

SO3Na SO3Na

H2N

minus

minus

+

+

minus

+

minus

+

ONO

80∘ 20 h

n










2SO4


2O5 followed by H

2SO4and








Acknowledgment


References






































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of





































NaMAEBA

Initiator system

MWNT

MWNT GL-NTx

Gel

Ultrasonication









H3C

H3C

CH3

CH3

NH2

CNTs

Gentamicin

O

O

O

O

O

O

O

O

minus

Ominus

Ominus

OH

OH

OH

HN

NH3+

NH2+

NH3+








NH2

SO3H

SO3H

SO3Na

SO3Na

SO3Na SO3Na

H2N

minus

minus

+

+

minus

+

minus

+

ONO

80∘ 20 h

n










2SO4


2O5 followed by H

2SO4and








Acknowledgment


References






































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of

























NaMAEBA

Initiator system

MWNT

MWNT GL-NTx

Gel

Ultrasonication









H3C

H3C

CH3

CH3

NH2

CNTs

Gentamicin

O

O

O

O

O

O

O

O

minus

Ominus

Ominus

OH

OH

OH

HN

NH3+

NH2+

NH3+








NH2

SO3H

SO3H

SO3Na

SO3Na

SO3Na SO3Na

H2N

minus

minus

+

+

minus

+

minus

+

ONO

80∘ 20 h

n










2SO4


2O5 followed by H

2SO4and








Acknowledgment


References






































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of













NaMAEBA

Initiator system

MWNT

MWNT GL-NTx

Gel

Ultrasonication









H3C

H3C

CH3

CH3

NH2

CNTs

Gentamicin

O

O

O

O

O

O

O

O

minus

Ominus

Ominus

OH

OH

OH

HN

NH3+

NH2+

NH3+








NH2

SO3H

SO3H

SO3Na

SO3Na

SO3Na SO3Na

H2N

minus

minus

+

+

minus

+

minus

+

ONO

80∘ 20 h

n










2SO4


2O5 followed by H

2SO4and








Acknowledgment


References






































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


NaMAEBA

Initiator system

MWNT

MWNT GL-NTx

Gel

Ultrasonication









H3C

H3C

CH3

CH3

NH2

CNTs

Gentamicin

O

O

O

O

O

O

O

O

minus

Ominus

Ominus

OH

OH

OH

HN

NH3+

NH2+

NH3+








NH2

SO3H

SO3H

SO3Na

SO3Na

SO3Na SO3Na

H2N

minus

minus

+

+

minus

+

minus

+

ONO

80∘ 20 h

n










2SO4


2O5 followed by H

2SO4and








Acknowledgment


References






































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


H3C

H3C

CH3

CH3

NH2

CNTs

Gentamicin

O

O

O

O

O

O

O

O

minus

Ominus

Ominus

OH

OH

OH

HN

NH3+

NH2+

NH3+








NH2

SO3H

SO3H

SO3Na

SO3Na

SO3Na SO3Na

H2N

minus

minus

+

+

minus

+

minus

+

ONO

80∘ 20 h

n










2SO4


2O5 followed by H

2SO4and








Acknowledgment


References






































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


NH2

SO3H

SO3H

SO3Na

SO3Na

SO3Na SO3Na

H2N

minus

minus

+

+

minus

+

minus

+

ONO

80∘ 20 h

n










2SO4


2O5 followed by H

2SO4and








Acknowledgment


References






































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of






2SO4


2O5 followed by H

2SO4and








Acknowledgment


References






































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


























































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of






















































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of




















































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of



















































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


















Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of





Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of

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