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Polymer Degradation and Stability xxx (2014) 1e8
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Polymer Degradation and Stability
journal homepage: www.elsevier .com/locate /polydegstab
Inclusion of PLLA nanoparticles in thermosensitivesemi-interpenetrating polymer networks
Nicoletta Rescignano a,*, Rebeca Hernández a, Ilaria Armentano b, Debora Puglia b,Carmen Mijangos a, José Maria Kenny a,b
a Instituto de Ciencia y Tecnología de Polimeros, ICTP-CSIC, Juan de la Cierva 3, 28006 Madrid, SpainbMaterials Engineering Center, UdR INSTM, University of Perugia, Strada di Pentima 4, 05100 Terni, Italy
a r t i c l e i n f o
Article history:Received 5 December 2013Received in revised form3 February 2014Accepted 3 March 2014Available online xxx
Keywords:HydrogelNanoparticlesNanocompositePorous structureThermal stability
* Corresponding author. Tel.: þ34 912587424.E-mail addresses: [email protected], nicoresci@
http://dx.doi.org/10.1016/j.polymdegradstab.2014.03.00141-3910/� 2014 Elsevier Ltd. All rights reserved.
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a b s t r a c t
Novel nanocomposite semi-interpenetrating (semiIPN) polymer networks of poly(N-isopropylacrylamide) (PNIPAAm) and alginate (Alg-PNIPAAm), containing poly-L-lactide (PLLA) nano-particles were prepared and morphological, thermal, chemical, thermomechanical and rheologicalproperties were investigated.
The successful incorporation of PLLA nanoparticles into the semiIPN gels was confirmed by fieldemission scanning electron microscope (FESEM) and infrared spectroscopy (FT-IR). FESEM microscopyalso showed the different pore size and pore size distribution of the nanocomposite respect to theprimary gel. The resulting morphology was related to the thermal and viscoelastic properties exhibitedby the materials. The introduction of PLLA nanoparticles does not affect the thermal stability of the geland does not modify the lower critical solution temperature (LCST), while interferes with the contractionbehavior of the gel, leading to a different thermal expansion coefficient observed for the nanocomposite.Furthermore, rheological results suggest a different degree of crosslinking for the nanocomposite gel, dueto the presence of PLLA nanoparticles that probably hinders the reaction of crosslinking of PNIPAAm. Theprepared NPs-AlgPNIPAAm-semiIPN gels with thermosensitive and biodegradable properties are veryinteresting from both applied and fundamental perspectives and make this system a good candidate forpractical application in drug delivery and controlled drug release.
� 2014 Elsevier Ltd. All rights reserved.
1. Introduction
Thermosensitive hydrogels based on poly (N-iso-propylacrylamide) (PNIPAAm) or related copolymers represent themost extensively studied stimulus-sensitive polymer hydrogelmaterials for biomedical applications [1e4]. PNIPAAm hydrogel inaqueous solution exhibits a rapid and reversible hydrationedehy-dration change in response to small temperature changes aroundits lower critical solution temperature (LCST) [5,6]. The gel forms adense polymer skin layer at the surface when a swelling PNIPAAmhydrogel is immersed in water above the LCST [7,8]. One of theproblems in applying conventional PNIPAAm hydrogels is that theresponse rate to temperature changes is very slow, which restrictswider applications, such as on-off valves, artificial muscles or drugdelivery applications [9]. One strategy to overcome this drawback isthe combination of crosslinked PNIPAAm with a natural polymer
gmail.com (N. Rescignano).
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no N, et al., Inclusion of PLLy (2014), http://dx.doi.org/10
such as alginate in the form of a semi-interpenetrating polymernetwork. The resulting material presents an increased deswellingrate with respect to raw poly(NIPAAm), due to an increasedporosity promoted during the reaction of crosslinking of the N-isopropylacrylamide monomer in the presence of alginate [10e12].Alginate, a polysaccharide extracted from seaweeds, is consideredas one of the most versatile biopolymers for biomedical applica-tions [13e15]. In recent years, different methods of fabricatingalginate/PNIPAAm hydrogels have been developed, in which thecombination of the advantages of synthetic and natural polymershas been taken into account. Kim et al. [16] and Ju et al. [17] pre-pared two kinds of hydrogels based on an amino semitelechelicPNIPAAm and cross-linked alginate with Ca2þ. The grafting ofNIPAAm hydrophobic chains into hydrophilic alginate providesfurther functionalities to the resulting temperature responsive gels[18,19].
The incorporation of PNIPAAm nanoparticles into PNIPAAmhydrogels is another strategy to increase the response rate of PNI-PAAm hydrogels to temperature. The result may be ascribed to the
A nanoparticles in thermosensitive semi-interpenetrating polymer.1016/j.polymdegradstab.2014.03.007
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generation of pores that allow water molecules to be quicklysqueezed out of the bulk [20].
The addition of polymer nanoparticles into polymer gels alsoallows the local delivery of hydrophobic drugs when these areloaded into hydrophobic particles. These nanoparticle networkshave several advantages over the conventional bulk hydrogels forcontrolling the release of high molecular weight biomolecules. Thedrug would diffuse out firstly from the particles to the hydrogelnetwork, then further being released from the bulk hydrogelnetwork; so, in the case of nanocomposite hydrogel, two barrierscontrol the drug release compared with the bulk PNIPAAmhydrogel or pure particles [21,22].
One of themost commonly usedmaterials for the preparation ofcarriers for the delivery of pharmacological agents is poly-L-lactide(PLLA), that it is well known to be biocompatible, biodegradableand approved by the Food and Drug Administration (FDA) [23,24].PLLA microparticles can be prepared by single emulsion or doubleemulsion methods [25,26]. Although there is a large number ofstudies on the controlled release of various drugs from a PLLApolymer matrix [27e29], only few studies have been performed onthe controlled release of hydrophobic drugs through a hydrophilichydrogel matrix. Some examples of PLLA embedded hydrogelsinclude alginate [30], gelatin [31], pluronic [32] or chitosan [33].
In this research, we report on the preparation and character-ization of a novel nanocomposite hydrogel prepared by the incor-poration of biocompatible and biodegradable PLLA nanoparticlesinto semi-interpenetrating polymer hydrogels of a natural polymersuch as alginate and thermosensitive PNIPAAm. This strategy al-lows obtain materials with an improved response to temperaturewith respect to pure PNIPAAm hydrogels suitable to be employed indrug delivery applications as PLLA nanoparticles are able toencapsulate different pharmacological agents and release them in acontrolled way.
2. Experimental part
2.1. Materials
PLLA (I.V.0.9e1.20 dL/g) was used as constituent for the NPformation. Polyvinyl alcohol (PVA) (31,000e50,000 g/mol 87e89%hydrolyzed) was used as surfactant and chloroform (CHCl3) fromSigma Aldrich as solvent. The N-isopropylacrylamide (NIPAAm)(Panreac), the initiator potassium persulphate (Fluka), the cross-linker N,N methylene bisacrylamide (Bis) (Sigma Aldrich), and theaccelerator N,N,N,N-tetramethylethylenediamine (TEMED) (BioRad) were used as received. Alginic acid sodium salt from brownalgae with a 65e70% guluronic acid was purchased from SigmaAldrich and used as received. Alginate stock solutions were pre-pared by dissolving alginate powder in distilled water to yield 1 gper 100 ml solution.
2.2. Methods
The PLLA nanoparticles (NPs) were prepared by the doubleemulsion (water/oil/water) method, with subsequent solventevaporation as reported elsewhere [26]. Briefly, PLLAwas dissolvedin CHCl3 by magnetic stirring. This solution was emulsified withphosphate buffered saline solution (PBS) using the tip sonicator(VIBRA CELL Sonics mod. VC750). The resulting emulsion was thenmixed with 2% wt/v of PVA aqueous solution, by sonication treat-ment, for the formation of second emulsion. In order to remove thesolvent, the second emulsion was transferred in 0.2% wt/v of PVAaqueous solution and was magnetically stirred over night at roomtemperature. The nanoparticles were collected by centrifugationand washed four times with distilled water.
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Two kinds of gels were prepared, the first one is a semi-interpenetrating polymer network consisting of alginate andcrosslinked PNIPAAm (AlgPNIPAAm-semiIPN) and the second one isa nanocomposite gel in which PLLA NPs are encapsulated into thesemiIPN (NPs-AlgPNIPAAm-semiIPN). Both materials were obtainedby polymerization of NIPAAm and Bis in a 1% wt alginate aqueoussolution. In the case of the nanocomposite gel, PLLA NPs (1% wt)were dispersed in alginate solution. The selection of this specificpercentage is due to the requirement of correct nanofiller dispersioninside the matrix, since with a high percentage of NPs the hydrogelpresents an inhomogeneous morphological structure (data notshown). After that, the polymerization was initiated by the potas-sium persulphate/TEMED redox system in nitrogen atmosphere andcarried out at room temperature. Solutions were poured into Petridishes and allowed to react at room temperature for 24 h. The ob-tained samples were dialyzed against fresh water and finally theywere lyophilized [10]. A schematic representation of the procedureutilized for the preparation of the IPNs is shown in Fig. 1.
The morphologies exhibited by AlgPNIPAAm-semiIPN gels andNPs-AlgPNIPAAm-semiIPN were observed in a field emissionscanning electron microscope (FESEM Supra 25, Zeiss). Cryo-crosssections of the systems were sputtered with a gold coated by anAgar automatic sputter coating and then analyzed.
Swelling ratios (SR) of gels were measured gravimetrically afterwiping off water on the surface with moistened filter paper at therange temperature of 25, 32, 37 and 48 �C. Gel samples wereincubated in distilled water for at least 24 h at each temperature. SRis defined as follows:
SR ¼ Ws=Wd (1)
where Ws is the weight of the water in the swollen gel at theparticular temperature and Wd is the dry weight of the gel.
The deswelling kinetics of gels was measured gravimetrically at37 �C after wiping off water on the surface with moistened filterpaper. Before the measurement, the gel samples reached equilib-rium in distilled water at room temperature. The weight changes ofgels were recorded at the course of deswelling at regular timeintervals.
Water retention (WR) is defined as follows:
WR ¼ 100� ðWt�WdÞ=Ws (2)
where Wt is the weight of the gel at regular time intervals and theother symbols are the same as defined above.
The chemical structures of the obtained IPNs were examinedwith a Fourier infrared spectroscopy (FT-IR), using Jasco FT-IR 615spectrophotometer in attenuated total reflection mode (ATR) in the400e4000 cm�1 range, with a 4 cm�1 resolution.
Calorimetric analysis was performed (DSC, Mettler Toledo 822/e), in order to determine the LCST temperature: this set of experi-ments was performed from 20 to 40 �C at a heating rate of 2 �C/min,under nitrogen atmosphere on the swollen gels. All samples wereequilibrated in distilled water at 15 �C for at least 24 h prior to theexperiments. The transition temperature was defined as the tem-perature corresponding to the peak of the thermogram. The onsettemperaturewas determined from crossing of the baselinewith theleading edge of the endotherm. Three independent determinationswere performed for each sample.
Thermogravimetric analysis (TGA) was performed on 10 mgsamples on an Exstar 6300 TGA quartz rod microbalance in nitro-gen atmosphere from 30 to 500 �C, at 10 �C/min. Thermomechan-ical characterization was carried out by TMA 7, Perkin Elmer, usingan expansion probe performing a heating scan from 12 to 65 �C, at arate of 10 �C/min. Following this first scan, a cooling step in the
LA nanoparticles in thermosensitive semi-interpenetrating polymer.1016/j.polymdegradstab.2014.03.007
Fig. 1. Schematic representation of the procedure utilized for the preparation of the AlgPNIPAAm-semiIPN and NPs-AlgPNIPAAm-semiIPN.
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same range of temperature and at same rate was applied, and thena second heating scan from 12 to 65 �C at a rate of 10 �C/min wasapplied on the same sample. The evaluation of expansion/contraction coefficient was done on the normalized deformationversus temperature curves.
Dynamic viscoelastic measurements were performed in a TAInstruments AR1000 Rheometer, using the 20 mm steel parallelplate to measure the storagemodulus, G0, the loss modulus, G00, andthe loss tangent, tan d. The linear viscoelastic region was locatedwith the aid of a torque sweep and a constant torque value of 5Frequency scans between 0.01 and 10 Hz were carried out inisothermal conditions (T¼ 37 �C). To avoid the evaporation of waterin the course of the rheological measurements, a solvent trap fromTA Instruments was used.
3. Results and discussion
3.1. Morphological characterization
FESEM was carried out in order to characterize the effect of thePLLA nanoparticle incorporation on the pore size and on the poresize distribution of the resulting nanocomposites.
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Fig. 2 shows the morphology of the voids in AlgPNIPAAm-semiIPN (Fig. 2a and b) and in NPs-AlgPNIPAAm-semiIPN (Fig. 2cand d) at two different magnifications. In Fig. 2b the inset repre-sents the magnification of the nanopores. The gel presents a het-erogeneous pore distribution with two pore size distributionswith macropore (200 mm) and nanopore (<1 mm) structure situ-ated in the macropore walls. In the nanocomposite system it isevident from the FESEM micrographs that PLLA nanoparticleincorporation has significant effect on the overall micro-architecture of the system. The high porosity of these samples canbe partly explained by the preparation procedure. The initial phaseof hydrogel synthesis encompassed 24 h polymerization andcrosslinking of PNIPAAm in the presence of sodium alginate.During this period, electrostatic repulsions among carboxylateanions of alginate chains contribute to the expansion of formingnetwork [10].
The different porous structure of NPs-AlgPNIPAAm-semiIPNwas probably due to the presence of nanoparticles during the for-mation of gel. The FESEM images reveal that the loading of nano-spheres reduced the pore size and uniformity of the pore structure[31]. A similar behavior was described by Serizawa et al. andKaneko et al. that prepared porous PNIPAAm hydrogels having a
A nanoparticles in thermosensitive semi-interpenetrating polymer.1016/j.polymdegradstab.2014.03.007
Fig. 2. FESEM images of AlgPNIPAAm-semiIPN (a and b) and NPs-AlgPNIPAAm-semiIPN (c and d).
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rod shape obtained by the incorporation of silica micro- and nano-particles to control the pore size [34,35].
A further magnification of the FESEM image corresponding tothe nanocomposite gel can be observed in Fig. 3, demonstratingthat the PLLA NPs are distributed on the pore walls and in the innerpart of the pores. Fig. 3b shows an FESEM image corresponding toPLLA NPs that present a particle size distribution with an averagediameter of 180 nm, as previously reported [26].
3.2. Swelling behavior
PNIPAAm is the most popular temperature-responsive polymersince it exhibits a sharp phase transition in water with a lowercritical solution temperature (LCST) at around 32 �C [36]. Fig. 4shows the swelling ratios of NPs-AlgPNIPAAm-semiIPN and of
Fig. 3. FESEM images of NPs-AlgPNIPAAm-semi
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AlgPNIPAAm-semiIPN. According to the obtained results, no dif-ference in terms of swelling behavior was detected with the addi-tion of NPs.
The kinetics of deswelling was also monitored; specifically thesamples were transferred from the swollen state at room temper-ature into distilled water at 37 �C (Fig. 5). Also in the case ofdeswelling, the same behavior for both systemswas observed, witha similar water loss of 60% of the gels after 5 min. So the incorpo-ration of PLLA NPs does not influence the deswelling kinetics.
3.3. Chemical characterization
The incorporation of PLLA NPs into AlgPNIPAAm-semiIPNs wasfurther confirmed through FT-IR in ATRmode, as shown in Fig. 6. Aspreviously reported [37], in the FT-IR spectrum corresponding to
IPN fracture (a) and PLLA nanoparticles (b).
LA nanoparticles in thermosensitive semi-interpenetrating polymer.1016/j.polymdegradstab.2014.03.007
Fig. 4. Temperature dependence of the equilibrium swelling ratio of AlgPNIPAAm-semiIPN gel and NPs-AlgPNIPAAm-semiIPN.
Fig. 6. Fourier-transform infrared spectroscopy (FT-IR) of AlgPNIPAAm-semiIPN, PLLANPs and NPs-AlgPNIPAAm-semiIPN.
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AlgPNIPAAm-semiIPN, the peak located at 1647 cm�1 can beassigned to the amide carbonyl group stretching vibration and thepeak at 1551 cm�1 indicates the NH deformation vibration in theamide groups.
Finally, the sharp peaks at 1387 and 1367 cm�1 correspond tothe characteristic absorbance of isopropyl in PNIPAAm [37]. The IRspectrum of the gel exhibited strong absorption at 3425 cm�1 thatwe assign to stretching vibration of the hydroxyl groups (eOH). TheFT-IR spectrum corresponding to the nanocomposite NPs-AlgPNIPAAm-semiIPN shows a new peak at 1754 cm�1 attributedto the stretching vibration of C]O and the absorption peaks of CeOat 1045 cm�1 and 1085 cm�1 of ester in PLLA (Fig. 6).
3.4. Thermal behavior
Fig. 7a and b illustrates TG (mass loss) and DTG (derivative massloss) curves of AlgPNIPAAm-semiIPN and the system containingPLLA NPs; the profile of weight loss for PLLA NPs is also reported, inorder to verify the effect of introduction of the PLLA nanoparticleson the thermal stability of the filled system. Both samples show asubstantially similar trend: the DTG curve of AlgPNIPAAm-semiIPN,beyond the transition due to the loss of freely bound water, showsanother thermal event in the temperature around 410 �C, which is
Fig. 5. Deswelling kinetics of AlgPNIPAAm-semiIPN and NPs-AlgPNIPAAm-semiIPN.
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attributed to the one-step degradation of the synthetic polymer[38]. The introduction of PLLA nanoparticles does not affect thethermal stability of the gel, since no reduction in the temperature ofthe main peak was measured. Only a weak shoulder at lowertemperature around 366 �C can be detected and attributed to thepresence of PLLA nanoparticles in the nanocomposite. The residualmass at the end of the test is slightly increased (from 1.32% wt ofneat AlgPNIPAAm-semiIPN up to 1.92% wt of NPs-AlgPNIPAAm-semiIPN nanocomposite) due to the presence of char residuefrom degradation of PLLA, in agreement with data reported in theliterature [39]. The AlgPNIPAAm-semiIPN thermogram presentstwo steps: the first step between 25 and 150 �C is mainly attributedto water, the second at 368e420 �C is attributed to the decompo-sition of PNIPAAm [38].
The nanocomposite with biodegradable nanoparticles showsthe same behavior of the AlgPNIPAAm-semiIPN, indicating that thePLLA NPs do not affect the thermal behavior of the gel.
Fig. 8 shows DSC thermograms of gels and the curves arerepresentative of three repeated tests. PNIPAM/water mixturesdemix upon heating and this phase separation process is accom-panied by an endothermic heat effect. The temperature at whichthis effect occurs is known as low critical solution temperature(LCST). Further heating of AlgPNIPAAm-semiIPN up to highertemperatures could induce partial vitrification of the PNIPAAmphase. The DSC thermograms of swollen AlgPNIPAAm-semiIPN andnanocomposite NPs-AlgPNIPAAm-semiIPN in Fig. 8 shows theappearance of an endotherm peak for both samples. Here, thetemperatures at the maxima of the DSC endotherms were referredto as the LCST of the gels. As can be observed, no significant dif-ferences among the LCST of both materials are obtained, being theLCST for AlgPNIPAAm-semiIPN, 36.2� 0.4 �C whereas in the case ofthe nanocomposite NPs-AlgPNIPAAm-semiIPN, the LCST isT ¼ 35.1 � 0.5 �C. This result is in agreement with previous resultsregarding AlgPNIPAAm-semiIPNs [36].
Deshmukh et al. [40] observed a sharp transition of poly(N-isopropylacrylamide) (PNIPAM) inwater at 32 �C, this phenomenonis due to a transition from a hydrophilic state below this temper-ature to a hydrophobic state above it, at the same time the hydrogelpresents a shrinking and releases the solvent (water) into the sur-rounding medium. They believe that this fact is caused by entropicgain of water molecules, when they are released into the waterphase for the temperature increase. This means that the LCST isassociated with the region in the phase diagram at which the
A nanoparticles in thermosensitive semi-interpenetrating polymer.1016/j.polymdegradstab.2014.03.007
Fig. 7. TGA (a) and DTG curves (b) of NPs-AlgPNIPAAm-semiIPN, PLLA NPs and AlgP-NIPAAm-semiIPN.
Fig. 8. DSC heating scan of AlgPNIPAAm-semiIPN and NPs-AlgPNIPAAm-semiIPN.
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enthalpic contributions of the water, hydrogen-bonded to thepolymer chain, become less than the entropic gain of the system asa whole (water disassociated from the polymer). This behaviordepends on the hydrogen-bonding capabilities of monomer units,and accordingly, it is believed that the LCST of a particular polymercan be controlled with a variation of the ratio of the hydrophilic tothe hydrophobic content. In the case of the semiIPN containing thePLLA nanoparticles, the relative small amount of NPs, even if itmodifies the thermal contraction of the whole system for a reducedcrosslinking density, does not affect the total hydrophilicity of thesystem; consequently, no substantial deviation on the LCST hasbeen detected in the case of NPs containing gel [40].
In Fig. 9, the TMA curves corresponding to AlgPNIPAAm-semiIPN and nanocomposite NPs-AlgPNIPAAm-semiIPN areobserved, for the first (a) and the second heating scans (b). The firstheating scan (Fig. 9a) reveals a different contraction of the nano-composite with respect to the neat gel after the LCST. While asubstantial analogy and overlapping in the thermal behavior can beobserved up to the transition, a deviation can be seen for thenanocomposite system after the LCST. The trend for TMA curves canbe explained considering the different general behavior ofAlgPNIPAAm-semiIPN if considered in the wet or dry phase. TheAlgPNIPAAm-semiIPN gel exhibits a volume phase transition at theLCST, which causes a sudden change in the solvation state. Such
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polymer, hydrophilic below the LCST, becomes insoluble and hy-drophobic upon heating. While no significant interaction betweenpolymer and the suspended nanoparticles can be detected belowLCST, interactions could occur between polymer and nanoparticlesabove this temperature, which lead to a different shrinkage of thepolymer. The LCST here detected as the point where a suddenvariation in the slope of the L/lo versus temperature curves isshown, represents the point where water is forced out of thehydrogel and hence a collapse of the hydrogel network structure isevident. In this state, the more evident contraction of theAlgPNIPAAm-semiIPN nanocomposite during the first heating scan(Fig. 9a) is due to the different pore structure in terms of dimensionand distribution. As it has been previously reported, a more ho-mogeneous and smaller pore size results in a faster and highercontraction in the case of temperature responsive hydrogels [16].
A different behavior is indeed observed in the second heatingscan of the gels (Fig. 9b), due to the previous heating made on thesamples up to 65 �C. Since the first heating scan was performed inthe region in which the NPs undergo their glass transition (57 �C[26]) and a variation on the morphology of the gel should beconsidered and expected after the collapse of the hydrogelnetwork, a different contraction during the second thermal scanwas recorded. The presence of thermally active PLLA nanoparticlesthat undergo their thermal transition and the possibility of afurther crosslinking reaction of the PNIPAAm gel could interferewith the contraction behavior of the nanocomposite: the observedbehavior in the second heating scan can be justified consideringthat both thermal modification of the PLLA nanoparticles andfurther crosslinking of the gel could take place after a first heatingscan up to 60 �C, leading to a reduced and delayed contraction (afterthe Tg of the NPs) of gel in presence of PLLA nanoparticles.
Fig. 10 shows the elastic and the loss modulus obtained for thesample AlgPNIPAAm-semiIPN and the nanocomposite gel as afunction of frequency. To be considered a gel, the systemmust meetsome requirements according to its rheological behavior: (i) itsdynamic elastic modulus (G0) must be relatively independent of thefrequency of deformation and (ii) G0 must be greater than G00 at allfrequencies. These two characteristics are observed in Fig. 10, whereboth samples present a gel-like behavior at T ¼ 20 �C which ischaracterized by the frequency-independence of G0 and G00, being G0
higher than G00 at all frequencies. As can be observed, the elasticmodulus encountered for the AlgPNIPAAm-semiIPN(G0 ¼ 320 � 30 Pa) is higher than that corresponding to the nano-composite NPs-AlgPNIPAAm-semiIPN (G0 ¼ 146 � 10 Pa).
LA nanoparticles in thermosensitive semi-interpenetrating polymer.1016/j.polymdegradstab.2014.03.007
Fig. 9. TMA curves of AlgPNIPAAm-semiIPN and NPs-AlgPNIPAAm-semiIPN related tothe first heating scan (a) and the second heating scan (b).
Fig. 10. Evolution of the elastic modulus G0 and the loss modulus G00 as a function offrequency for sample AlgPNIPAAm-semiIPN (closed symbols G0 (-) and G00(C)) andNPs-AlgPNIPAAm-semiIPN (open symbols G0 (,) and G00 (B)).
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This result might suggest a different degree of crosslinking forthe nanocomposite gel that might be due to the presence of PLLAnanoparticles that hinders the reaction of crosslinking of NIPAAmwith BIS as previously reported for other nanocomposite mate-rials [41]. Consequently, rheological properties of nanocompositegels are slightly reduced with the introduction of PLLAnanoparticles.
4. Conclusions
The inclusion of PLLA nanoparticles in thermosensitive semi-interpenetrating polymer networks of alginate and poly (N-iso-propylacrylamide) was successfully developed in this paper.
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The FESEM images revealed differences in the obtained porousstructure obtained, specifically; the incorporation of PLLA NPsresulted in a more homogeneous pore structure for the nano-composite than in the case of the neat gel, while NPs do not affectthe thermal stability of the gel.
The change in morphology has important consequences on thethermal properties, being the contraction of the material withtemperature much more evident for the case of the nanocompositesemiIPN than for the case of the neat semiIPN. Moreover, theintroduction of PLLA nanoparticles result in nanocomposite gelswith lower elastic modulus as the radical crosslinking reactionmight be hindered because of the presence of the nanoparticles.
The introduction of PLLA NPs in the AlgPNIPAAm-semiIPN ma-trix makes this system a good candidate for application incontrolled drug release systems, since biodegradable polymericnanoparticles are able to encapsulate different biological systemsand release them in a controlled way.
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LA nanoparticles in thermosensitive semi-interpenetrating polymer.1016/j.polymdegradstab.2014.03.007
