1 Advances in Polymer Science and Technology: An International Journal 2012; 2 (1): 1-15

Review Article

DRUG DELIVERY: SPECIAL EMPHASIS GIVEN ON BIODEGRADABLE POLYMERS.

Swati Aggarwal,* Achhrish Goel, Sandeep Singla

Department of pharmaceutics, M.M. College of pharmacy, Maharishi Markandeshwar University, Mullana, Ambala. (H.R.)

Correspondace author:- Swati Aggarwal* Department of pharmaceutics, M.M. College of Pharmacy, Maharishi

Markandeshwar University, Mullana, Ambala(H.R.)

Ph no- 09729905526

E mail: - swati15aggarwal@gmail.com

Received 29 January 2011; accepted 03 February 2011

Abstract

System of administering drug through controlled delivery so that an optimum amount reaches the target site. Drug delivery

system encompass the carrier, route, and target. Drug dosage forms contain many components in addition to the active

pharmaceutical ingredient(s) to assist in the manufacturing process as well as to optimize drug delivery. Due to advances in

drug delivery technology, excipients are currently included in novel dosage forms to fulfil specific functions and in some cases

they directly or indirectly influence the extent and/or rate of drug release and absorption. Since plant polysaccharides comply

with many requirements expected of pharmaceutical excipients such as non-toxicity, stability, availability and renewability

they are extensively investigated for use in the development of solid oral dosage forms. Polymers have been used as a main

tool to control the drug release rate from the formulations. Extensive applications of polymers in drug delivery have been

realized because polymers offer unique properties which so far have not been attained by any other materials. Advances in

polymer science have led to the development of several novel drug-delivery systems. These newer technological development

include drug modification by chemical means, career based drug delivery and drug entrapment in polymeric matrices or within

pumps that are placed in desired bodily compartments. These technical development in drug delivery/targeting approaches

improve the efficacy of drug therapy thereby improve human health. Biodegradable polymers have been widely used in

biomedical applications because of their known biocompatibility and biodegradability. In the biomedical area, polymers are

generally used as implants and are expected to perform long term service. These improvements contribute to make medical

treatment more efficient and to minimize side effects and other types of inconveniences for patients.

© 2011 Universal Research Publications. All rights reserved

Key words: Drug delivery, Biodegradable polymer, Factor Affecting Polymer.

Introduction:- Drug delivery is the method or process of

administering pharmaceutical compound to achieve a

therapeutic effect in humans or animals.[1,2]. Drug delivery

technologies modify drug release profile, absorption,

distribution and elimination for the benefit of improving

product efficacy, safety, as well as patient compliance and

convenience.

Novel drug delivery:- A novel drug delivery system is a

system that offer multiple drug delivery solutions such as:

Oral Drug Delivery Systems and Materials

Parenteral and Implant Drug Delivery Systems

Pulmonary and Nasal Drug Delivery

Transmucosal Drug Delivery

Transdermal and Topical Drug Delivery

Delivery of Proteins and Peptides

Drug Delivery Pipelines

Drug Delivery Deals

Polymers:- polymers are macromolecules having very large

chains, contain a variety of functional groups, can be blended

with low and high molecular weight materials. Polymers are

becoming increasingly important in the field of drug delivery.

Advances in polymer science have led to the development of

several novel drug delivery systems. A proper consideration

of surface and bulk properties can aid in the designing of

polymers for various drug delivery applications.[3].These

newer technological development include drug modification

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Advances in Polymer Science and Technology: An International Journal

Universal Research Publications. All rights reserved

2 Advances in Polymer Science and Technology: An International Journal 2012; 2 (1): 1-15

Table1. List of polymers used in drug delivery, [6-10]

by chemical means, career based drug delivery and drug

entrapment in polymeric matrices or within pumps that are

placed in desired bodily compartments. These technical

development in drug delivery approaches improve human

health. Use of polymeric material in novel drug delivery

approaches has attracted the scientists.[4]

Pharmaceutical application of polymers:- Used to achieve

taste masking, Use as a binder in tablets to viscosity and flow

controlling agent in liquids, suspension and emulsions.

Polymers can be used as film coating to disguise the

unpleasant taste of drug and to enhance drug stability and to

modify drug release characteristics.[5]

Natural polymers:- are described as below:-

Collagen:- Collagen is a major natural protein component in

mammals that is fabricated from glycine-proline-(hydroxy)

proline repeats to form a triple helix molecular structure [11].

So far, nineteen types of collagen molecules have been

isolated, characterized, and reported in both medical and

pharmaceutical applications [12-14]. Collagen has been

widely used in pharmaceutical applications due to the

fulfillment of many requirements of a drug delivery system

such as good biocompatibility, low antigenicity, and

degradability upon implantation [15]. Furthermore, collagen

gels are one of the first natural polymers to be used as a

promising matrix for drug delivery and tissue engineering

[16]. Biodegradable collagen-based systems have served as

3D scaffold for cell culture, survival of transfected

fibroblasts, and gene therapy [17, 18]. In this case, collagen

scaffolds were fabricated through introducing various

chemical cross-linking agents (i.e., glutaraldehyde,

formaldehyde, carbodiimide) or by physical treatments

(i.e., UV irradiation, freeze-drying, and heating) [19, 20–23].

Figure 1:- A schematic representation of collagen-based

liposome.(source; kang et al. [27] ).

Example:-The combination of liposomes and collagen-based

technologies has been long achieved since the early 80s [16].

In this case, drugs and other bioactive agents were firstly

encapsulated in the liposomes and then embedded inside a

depot composed of collagen-based systems, including

scaffolds and gels. The combination of these two

technologies (i.e., liposomes and collagen-based system) has

improved storage stability, prolonged the drug release rate,

and increased the therapeutic efficacy [11, 24, 25]. In

addition, a study that was conducted by Marston et al. [26],

demonstrated that temperature sensitive liposomes and

3 Advances in Polymer Science and Technology: An International Journal 2012; 2 (1): 1-15

collagen may thermally trigger the release of calcium and

phosphate salts. Multiple collagen-based system for

pharmaceutical carriers or medicinal applications are

currently available for clinical purposes [27]. Figure 1 depicts

a schematic representation of collagen-based liposome.

Gelatin:- Gelatin is a common natural polymer ( water

soluble polymer) or protein which is normally produced by

denaturing collagen [28]. It has been used in pharmaceutical

and medical applications due to its outstanding properties

such as biodegradability, biocompatibility, and low

antigenicity [29]. In addition, gelatin can be easy to

manipulate due to its isoelectric point that allows it to change

from negative to positive charge in an appropriate

physiological environment or during the fabrication, a

property that has found it being very attractive to many

pharmaceutical researchers [30]. Gelatin is one of the natural

polymers used as support material for gene delivery, cell

culture, and more recently tissue engineering. Gelatin-based

systems have the ability to control release of bioactive agents

such as drugs, protein, and dual growth factors [31, 29, 32]. It

has been reported that it is possible to incorporate liposome-

loaded bioactive compounds into PEG-gelatin gel which

function as porous scaffold gelatin-based temporary depots

with controlled drug release over prolonged periods of time

[33, 34]. However, some setbacks have been identified, and

they are said be associated with the use of gelatin-based

systems in pharmaceutical applications. These setbacks

include poor mechanical strength and ineffectiveness in the

management of infected sites [12].

Albumin:- Serum albumin was conjugated to poly-(ethylene

glycol) (PEG) and cross-linked to form mono-PEGylated

albumin hydrogels. These hydrogels were used as a basis for

drug carrying tissue engineering scaffold materials, based on

the natural affinity of various drugs and compounds for the

tethered albumin in the polymer network.

Alginate:- Alginate also serves as an example of a naturally

occurring linear polysaccharide. It is extracted from seaweed,

algae, and bacteria [35-37].The fundamental chemical

structure of alginate is composed of (1–4)-b-D-mannuronic

acid (M) and (1–4)-a-L-guluronic acid (G) units in the form

of homo polymeric (MM- or GG-blocks) and hetero

polymeric sequences (MG or GM-blocks) [38]. Alginate and

their derivates are widely used by many pharmaceutical

scientists for drug delivery and tissue engineering

applications due to its many unique properties such as

biocompatibility, biodegradability, low toxicity, non-

immunogenicity, water solubility, relatively low cost, gelling

ability, stabilizing properties, and high viscosity in aqueous

solutions [39,40]. Since alginate is anionic, fabrication of

alginate hydrogels has successively been achieved through a

reaction with cross-linking agents such as divalent or trivalent

cations mainly calcium ions, water-soluble carbodiimide,

and/or glutaraldehyde [41]. The cross-linking methodology

was conducted at room temperature and physiological pH

[42]. The success in fabricating highly porous 3D alginate

scaffolds has been through lyophilization [43]. Thus far,

alginate-based systems have been successfully used as a

matrix for the encapsulation of stem cells and for controlled

release of proteins, genes, and drugs [44-48]. In addition,

alginate-based systems have been used as depots for bioactive

agent-loaded liposomes, for slow drug release [49, 50].

Highly increased efficacy has been reported from these

integrated delivery systems when compared to polymeric-

based systems or liposome-based systems alone [51,52].

Dextran:- Dextran is a natural linear polymer of glucose

linked by a 1–6 linked-glucoyranoside, and some branching

of 1,3 linked side-chains [53]. Dextran is synthesized from

sucrose by certain lactic-acid bacteria, the best-known being

Leuconostoc mesenteroides and Streptococcus mutans. There

are two commercial preparations available, namely dextran

40 kilodaltons (kDa) (Rheomacrodex) and dextran 70

Kilodaltons (kDa) (Macrodex) [54,55]. In pharmaceutics,

dextran has been used as model of drug delivery due to its

unique characteristics that differentiate it from other

types of polysaccharide. This include water solubility,

biocompatibility, and biodegradability [56]. In recent studies,

dextran has been regarded as a potential polysaccharide

polymer that can sustain the delivery of both proteins,

vaccines, and drugs [57-60]. Interleukin-2, which is a highly

effective anticancer drug, is among the success obtained in

delivering a combination of drug-loaded liposome and

injectable dextran hydrogel [61]. Injectable and degradable

dextran-based systems for drug delivery were generated by a

cross-linking reaction with photo-polymerization or free

radical polymerization [62].

A study by Stenekes and coworkers [63] demonstrated the

successive encapsulation of a drug-loaded liposome depot

into a dextran polymer-based material. The polymeric-based

materials were fabricated using a two phase system, the first

phase was water and poly(ethylene glycol) and the second

one water methacyrlated dextran. The slower degradation of

dextran polymeric material resulted in sustained liposome

release over a period of 100 days [63]. Liposomes released

from depot were reported to be intact, and there was no

significant change in liposomal size. In a gene therapy study

by Liptay and coworkers [64], it was reported that

recombinant DNA (which contains chloramphenicol

acetyltransferase) was successively encapsulated in cationic

liposomes and then integrated within dextran. This system

was reported to be a suitable delivery system since it could

stop transfection efficiency within the colon epithelium wall

in vivo [64].

4 Advances in Polymer Science and Technology: An International Journal 2012; 2 (1): 1-15

Chitosan:- Chitosan is a natural polycationic copolymer

consisting of glucosamine and N-acetyl glucosamine units. It

is mostly obtained by deacetylation of chitin derived from the

exoskeleton of crustaceans. Chitosan has valuable properties

as biomaterials because it is considered to be biocompatible.

biodegradable, nontoxic. [65]. The cationic character and the

potential functional group make it an attractive biopolymer

for many biomedical and pharmaceutical application. As a

pharmaceutical excipient, chitosan has been used in many

formulations like powders, tablets, emulsions and gels.

Furthermore a controlled release of incorporated drugs can be

guaranted.[66, 67]. Chitosan also shows mucoadhesive

properties and antimicrobial properties.[68,69]. The bitter

taste of natural extracts such as caffeine has been masked

using chitosan. Chitosan can potentially be used as a drug

carrier, a tablet excipient, delivery platform for parenteral

formulations, disintegrant and tablet coating. From toxicity

and safety point, lower molecular weight chitosan (as an

oligosaccharide) has been shown to be safer with negligible

cytotoxicity on coca-2-cell. During the encapsulation process

using synthetic polymers, the protein is generally exposed to

the conditions which might cause their denaturation or

deactivation. Therefore a biocompatible alternative such as

chitosan is desirable for such applications. Gels based on

chitosan and ovalbumin protein have been suggested for

pharmaceutical and cosmetic use. Chotosan can also be

mixed with nonionic surfactant such as sorbitan ester to make

emulsion like solution s or creams.[70]. It is a promising

bioadhesive material at physiological PHs. This polymer

possesses OH and NH2 group that can give rise to hydrogen

bonding. These properties are considered essential for

mucoadhesion.[71, 72].One study accounts for possible use

of chitosan in mixtures of different ratios with anionic

polymers for the preparation of mucoadhesive tablets to be

used as a vaginal delivery system for metronidazole [73].By

the introduction of thiol groups to chitosan the mucoadhesive

properties could be strongly improved while maintaining its

biodegradability [74]. Chitosan was thereby modified by

attaching thioglycolic acid (TGA) onto the primary amino

groups of the polymer via an amide bond formation [75]. The

excellent bioadhesion could result in an increased residence

time of a drug at the site of absorption by interacting with the

mucosa [76, 77]. As chitosan is also known to exhibit

antimicrobial activity the chitosan-TGA conjugate would be

ideal as a matrix for the mainly cationic antimycotics for

treating mycotic infections in the vagina. A common

microbial problem in the vulvovaginal tract is the infection

with C. albicans [78]. Approximately 75% of women will

have a vaginal infection with a Candida strain during their

life and about 40–50% of them will suffer a second one and a

small percentage will show a chronic course [79]. By the

introduction of thiol groups the bioadhesive properties of

chitosan could be significantly improved. The addition of

clotrimazole led thereby to a further increase in bioadhesion

on mucosal tissue.

Cellulose Derivatives:- Cellulose is the most abundant

naturally occurring biopolymer [80, 81]. Various natural

fibers such as cotton and higher plants have cellulose as their

main constituent [82, 83]. It consists of long chains of

anhydro-D-glucopyranose units (AGU) with each cellulose

molecule having three hydroxyl groups per AGU, with the

exception of the terminal ends. Cellulose is insoluble in water

and most common solvents [81]; the poor solubility is

attributed primarily to the strong intramolecular and

intermolecular hydrogen bonding between the individual

chains [80]. In spite of its poor solubility characteristics,

cellulose is used in a wide range of applications including

composites, netting, upholstery, coatings, packing, paper, etc.

Chemical modification of cellulose is performed to improve

process ability and to produce cellulose derivatives

(cellulosics) which can be tailored for specific industrial

applications [84]. Large scale commercial cellulose ethers

include carboxymethyl cellulose (CMC), methyl cellulose

(MC), hydroxyethylcellulose (HEC), hydroxypropyl methyl

cellulose (HPMC), hydroxylpropyl cellulose(HFC), ethyl

hydroxyethyl cellulose (EHEC), and methyl hydroxyethyl

cellulose(MHEC).

Starch:- Plants synthesize and stored starch in their structure

as an energy reserve. It is generally deposited in the form of

small granules or cells with diameters between 1-100 µm.

After cellulose, starch is the most abundant carbohydrate

available from plant kingdom as raw material. The estimated

world production of starch amounts to 58 million tonnes,

extracted from maize (46 million), wheat (4.6 million),

potatoes (3.5 million), and the remainder coming from rice

and cassava roots (tapioca). Starch is the main carbohydrate

in plants and acts as a reserve food supply for periods of

growth, dormancy and germination. Being a biodegradable

polymer with well-defined chemical properties, it has a huge

potential as a versatile renewable resource for various

material applications in food and nonfood areas. The

composition and properties of commercial available starches

have been studied extensively. The properties of each starch

are strongly dependent on their plant source. Starch is a

heterogeneous polymer of α-D-glucose units. The anhydrous

glucose units (AGUs) are mainly linked by α-(1,4)-bonds and

to some extent by α-(1,6)-linkages. The biopolymer consists

of two distinguished structural forms: amylose and

amylopectin. Amylose is mainly found as a long linear

polymer containing about several hundred α-(1,4)-linked

glucose units (up to 6000 AGUs), with a molecular weight of

105-106 g mol-1. In the solid state, the chains very easily

form single or double helices. In contrast, amylopectin is a

highly branched molecule with a molecular weight of 107-

109 gmol-1. The branched polymer contains α-(1,4)-linked

glucose units but has additional α-(1,6)-glucosidic branching

points which are believed to occur every 10 to 60 glucose

units, i.e. 5% of the glucose moieties are branched.

5 Advances in Polymer Science and Technology: An International Journal 2012; 2 (1): 1-15

Fig 2:- Structures of (A) amylopectin or α- amylase and (B) β-amylose.

Modified starch was tested for general applicability of a new

pregelatinized starch product in directly compressible

controlled-release matrix systems. It was prepared by

enzymatic degradation of potato starch followed by

precipitation (retrogradation), filtration and washing with

ethanol. The advantages of the material include ease of tablet

preparation, the potential of a constant release rate (zero-

order) for an extended period of time and its ability to

incorporate high percentages of drugs with different

physicochemical properties. Release rates from retrograded

pre gelatinized starch tablets can be enhanced or decreased to

the desired profile by different parameters like geometries of

the tablet, compaction force and the incorporation of

additional excipients. [85].

Hyaluronic acid:- Hyaluronic acid (also called as

Hyaluronan and Hyaluronate (HA) and Sodium

Hyaluronate(SA) is sodium salt form of hyaluronic acid) is a

biodegradable, biocompatible, and viscoelastic linear

polysaccharide of a wide molecular weight range (1000 to

10,000,000 Da). It is a naturally occurring biopolymer, which

serves important biological functions in bacteria and higher

animals including humans. Naturally occurring hyaluronic

acid may be found in the tissue of higher animals, particularly

as intercellular space filler. It is found in greatest

concentrations in the vitreous humor of the eye and in the

synovial fluid of articular joints. [86]. Hyaluronic acid

comprises linear, unbranching, polyanionic disaccharide units

consisting of glucuronic acid (GlcUA) an N-acetyl

glucosamine (GlcNAc) joined alternately by β-1-3 and β-1-4

glycosidic bonds. Hyaluronic acid solutions are

characteristically viscoelastic and pseudoplastic. The

viscoelastic property of hyaluronic acid solutions that is

important in its use as a biomaterial is controlled by the

concentration and molecular weight of the hyaluronic acid

chains. As a microcapsule, it can be used for targeted drug

delivery. [87].

Cyclodextrin:- They are cyclic oligosaccharides consisting of

six to eight glucose units joined through α-1, 4 glucosidic

bonds. Cyclodextrins remains intact during their passage

throughout the stomach and small intestine of the GI tract.

However, in colon, they undergo fermentation in the presence

of vast colonic microfloras into small monosaccharide and

thus absorbed from these regions. [88, 90] β-cyclodextrins are

degraded to a very small extent in the small intestine but are

completely digested in the large intestine. Most bacterial

strains found abundantly in human beings are capable of

degrading cyclodextrins polysaccharide.

Biodegradable Polymer:- Biodegradation is a natural

process by which organic chemicals in the environment are

converted to simpler compounds, mineralized and

redistributed through elemental cycles such as carbon,

nitrogen and sulphur cycles. Biodegradable polymers have

been widely used in biomedical applications because of their

known biocompatibility and biodegradability. Biodegradable

polymers are intended for temporary aids, such as sutures,

tissue-supporting scaffolds, and drug delivery devices [90].

Polymers within this group retain their properties for a

6 Advances in Polymer Science and Technology: An International Journal 2012; 2 (1): 1-15

limited period of time and then gradually degrade into soluble

molecules that can be excreted from the body [91].

Biodegradable polymers are preferred for drug delivery

applications, since the need for surgical removal of the

depleted device is eliminated. Although the number of

biodegradable polymers is large, only a limited number of

polymers is suitable for drug delivery applications. Suitable

candidates must not only be biodegradable but also fit the

high prerequisites of biocompatibility. In addition, a polymer

should ideally offer processability, sterilizability, and storage

stability if it is to be useful for biomedical applications [92].

The greatest advantage of degradable polymers is that they

are broken down into biologically acceptable molecules that

are metabolized and removed from the body via normal

metabolic pathways. However, biodegradable materials do

produce degradation by-products that must be tolerated with

little or no adverse reactions within the biological

environment. These degradation products—both desirable

and potentially non desirable—must be tested thoroughly,

since there are a number of factors that will affect the

biodegradation of the original materials. The most important

of these factors are shown in the box below—a list that is by

no means complete, but does provide an indication of the

breadth of structural, chemical, and processing properties that

can affect biodegradable drug delivery systems.

Factor affecting biodegradation of polymers:-

Chemical structure.

Chemical composition.

Distribution of repeat units in multimers.

Presents of ionic groups.

Presence of unexpected units or chain defects.

Configuration structure.

Molecular weight.

Molecular-weight distribution.

Morphology (amorphous/semicrystalline,

microstructures, residual stresses).

Presence of low-molecular-weight compounds.

Processing conditions.

Annealing.

Sterilization process.

Storage history.

Shape.

Site of implantation.

Adsorbed and absorbed compounds (water, lipids,

ions, etc.).

Physicochemical factors (ion exchange, ionic

strength, pH).

Physical factors (shape and size changes, variations

of diffusion coefficients, mechanical stresses, stress-

and solvent-induced cracking, etc.).

Mechanism of hydrolysis (enzymes versus water).

Biodegradable polymers mainly investigated for drug

delivery applications are of either natural or synthetic origin.

Natural polymers, already we have discussed above.

Synthetic Polymers:-

Polyester:-

I). Polylactic acid (PLA):- PLA is thermoplastic

biodegradable polymer produced synthetically by

polymerization of lactic acid monomers or cyclic lactide

dimmers. Lactic acid is produced by fermentation of natural

carbohydrates for example, maize or wheat or waste products

from the agricultural or food industry. Commercial quantities

of PLA for packaging applications are produced through ring

opening polymerization of lactide, a reaction favoring the

formation of high molecular polymers. The final crystallioity

and mechanical properties of the polymer depends on the

stereochemistry of polymer backbone. PLA is degraded by

hydrolysis (the breaking of a chemical bond by adding water

to it) of the backbone esters of the polymer. The esters are

broken at random, so that the PLA chains in the material get

shorter and shorter until monomers of lactic acid start to

come loose and the plastic essentially dissolves. This process

is called ‗bulk degradation‘. PLA does not degrade by

microbial attack.

PLA is currently used in loose fill packaging, food packaging

films, thermoformed containers and short shelf life bottles.

PLA can be laminated to paper and paperboard by extrusion

coating for further use as packaging material. Drinking cups

and food containers for short shelf life products are other

application areas.

Fabrics produced from PLA provide a silky feel, durability,

and moisture-management properties. PEA is useful for

producing compost bags and disposable tableware also. PLA

has number of biomedical applications, such as sutures,

stents, dialysis media and drug delivery devices. General

structure of PLA as shown in fig. 3

Figure:-3

7 Advances in Polymer Science and Technology: An International Journal 2012; 2 (1): 1-15

II). Polyglycolic acid (PGA):- PGA is commonly obtained by

ring-opening polymerization of the cyclic diester of glycolic

acid, glycolide [93,94]. PGA is a hard, tough, crystalline

polymer with a melting temperature of ª225 °C and a glass

transition temperature, Tg, of 36 °C [93]. Unlike closely

related polyesters such as PLA, PGA is insoluble in most

common polymer solvents [93]. PGA has excellent fiber-

forming properties and was commercially introduced in 1970

as the first synthetic absorbable suture under the trade name

Dexon™ [93]. The low solubility and high melting point of

PGA limits its use for drug delivery applications, since it

cannot be made into films, rods, capsules, or microspheres

using solvent or melt techniques. General structure of PGA is

shown in fig. 4

Figure:- 4

III). Polyhydroxybutyrate (PHB):- PHB is a biopolymer,

which is present in all living organisms. Many bacteria

produce PHB in large quantities as storage material. It is not

toxic and is totally biodegradable. The polymer is primarily a

product of carbon assimilation (from glucose or starch) and is

employed by microorganisms as a form of ‗energy storage

molecule‘ to be metabolized when other common energy

sources are not available. PHB and its copolymers have

attracted much attention because they are produced

biosynthetically from renewable resources. Microcapsules

from PHB has been prepared by various techniques and

investigated for the release of bovine serum albumin [95].

PHB has also been suggested as a suitable matrix for drug

delivery in veterinary medicine, for instance in the rumen of

cattle [96].

IV). Poly(lactide-co-glycolide), PLGA:- Among the co-

polyesters investigated, extensive research has been

performed in developing a full range of PLGA polymers.

Both L- and DL-lactides have been used for co-

polymerization. The ratio of glycolide to lactide at different

compositions allows control of the degree of crystallinity of

the polymers.

[97]. When the crystalline PGA is co-

polymerized with PLA, the degree of crystallinity is reduced

and as a result this leads to increases in rates of hydration and

hydrolysis. It can therefore be concluded that the degradation

time of the copolymer is related to the ratio of monomers

used in synthesis. In general, the higher the content of

glycolide, the quicker the rate of degradation. However, an

exception to this rule is the 50:50 ratio of PGA: PLA, which

exhibits the fastest degradation. [98, 99]. PLGA is used in

drug delivery applications. Non-steroidal anti-inflammatory

drugs, e.g., diflunisal [100] and diclofenac sodium [101, 102],

have been incorporated into PLGA microspheres and

investigated for the treatment of rheumatoid arthritis,

osteoarthritis, and related diseases. The encapsulation of bio

macromolecules, e.g., proteins and vaccines, into polymeric

microspheres presents a formidable problem because of the

delicacy of these agents; bioactivity might be lost during

preparation, and the release may be poor due to adsorption

and/or aggregation. For instance, the release of recombinant

human interferon-g from PLGA microspheres was

incomplete and the instability of the system limited its use to

7 days or less [103]. Similarly, incomplete release of

lysozyme, recombinant human growth hormone, and a nerve

growth factor from PLGA microspheres was reported [104,

105, 106]. Hence, much effort has been spent in evaluating

PLGA delivery systems, with special regard to microsphere

preparation, protein stability, and release characteristics.

Model proteins studied include bovine serum albumin,

lysozyme, transferrin, and trypsin [107, 104, 108]. Several

peptides, including vapreotide and rismorelin porcine, have

been successfully incorporated and released from PLGA

microspheres [109–111]. Systems for the controlled release

of antigens have a great potential as vaccine adjuvants [112,

113, 108]. Recently, several studies of controlled release

systems for DNA have been presented. DNA of different

sizes has successfully been incorporated into PLGA

microspheres but the loss of DNA integrity and activity still

remains an important issue to be solved for these systems

[114, 115-117]. General structure of PLGA is shown in fig. 5

Figure:-5

V). Poly(e-caprolactone), PCL:- PCL is obtained by ring-

opening polymerization of the 6-membered lactone,e-

caprolactone (e-CL). Anionic, cationic, coordination, or

radical polymerization routes are all applicable [118].

Recently, enzymatic catalyzed polymerization of e-CL has

been reported [119, 120]. PCL crystallizes readily due to the

regular structure and has a melting temperature of 61 °C. It is

tough and flexible [118]. The Tg of PCL is low (–60 °C).

Thus, PCL is in the rubbery state and exhibits high

permeability to low molecular species at body temperature.

These properties, combined with documented

biocompatibility, make PCL a promising candidate for

controlled release applications [121]. PCL degradation

proceeds through hydrolysis of backbone ester bonds as well

8 Advances in Polymer Science and Technology: An International Journal 2012; 2 (1): 1-15

as by enzymatic attack. Hence, PCL degrades under a range

of conditions, biotically in soil, lake waters, sewage sludge,

in vivo, and in compost, and abiotically in phosphate buffer

solutions [122-125]. Hydrolysis of PCL yields 6-

hydroxycaproic acid, an intermediate of the w-oxidation,

which enters the citric acid cycle and is completely

metabolized. Hydrolysis, however, proceeds by homogeneous

erosion at a much slower rate than PLA and PLGA [125].

Hydrolysis of PCL is faster at basic pH and higher

temperatures [118]. PCL hydrolyzes slowly compared to PLA

and PLGA, it is most suitable for long-term drug delivery.

Capronor®, a 1-year contraceptive represents such a system

[118].

VI). Polydioxanone(PDS):- Although biodegradable

polylactides and glycolides have been used to develop

versatile resorbable multi-filament structures, there is

growing research involved in the development of materials

that form monofilament sutures. Multifilament sutures have a

higher risk of infection associated with their use and cause a

greater amount of friction when penetrating tissues. [126,

127]. Polydioxanone (referred to as PDS) is made by a ring-

opening polymerization of thep-dioxanone monomer. It is

characterized by a glass transition temperature in the range of

–10 to 0°C and a degree of crystallinity of about 55%.

Materials prepared with PDS show enhanced flexibility due

to the presence of an ether oxygen within the backbone of the

polymer chain. When usedin vivo, it degrades into monomers

with low toxicity and also has a lower modulus than PLA or

PGA. For the production of sutures, PDS is generally

extruded into fibers at the lowest possible temperature, in

order to avoid its spontaneous depolymerization back to the

monomer. General Structure of Polydioxanone is shown in

fig. 6

Figure:-6

Polyanhydrides:- Poly anhydride are class of

biodegradable polymer characterized by anhydride

bonds that connect repeat unit of polymers backbone

chain. Poly(anhydride-esters) are polymeric

compounds consisting of salicylic acid moieties

bridged by linker structures. An example of the

polymer structure is shown in Figure 7. These

compounds contain two types of important bonds -

anhydride and ester bonds shown in Figure 7 in blue

and red respectively. In the presence of water, both

bonds may degrade hydrolytically, releasing

salicylic acid (B) and sebacic acid (C). Salicylic acid

(B) is the active form of aspirin, an anti-

inflammatory agent, and sebacic acid is currently

used in drug delivery systems (Brem et al., 1995). In

vivo mice studies have indicated that this polymer

assists in wound healing and that it promotes bone

growth (Macedo, 1999).

The release of salicylic acid (B) via bond hydrolysis opens

up a variety of possibilities for creating drug delivery

systems. Potential applications include treatment of

inflammatory bowel disease, dental implants, and tissue

scaffolding. The studies on the degradation rate, the rate of

release of salicylic acid as a function of pH, have shown that

this polymer takes three months to degrade in acidic and

neutral environment, but at basic pH it degrades in 19-40

hours (Erdmann and Uhrich, 1999). Since the upper

gastrointestinal tract is acidic or neutral, this polymeric drug

can reach the intestines undamaged, and release salicylic acid

directly to the lower intestinal tract to treat the disease.

Aspirin is also used in dentistry, for example, in cases of

tooth breakage when there cannot be an immediate operation.

In this procedure, the fast influx of salicylic acid irritates the

surrounding tissue. Slower release of the medication,

provided by the poly(anhydride-esters) would be a gentler

solution.

A drawback to the poly(anhydride-ester) structure shown

in Figure 7 is its low Tg (glass transition temperature). This is

a temperature at which a polymer goes from a solid into a

rubbery state. The Tg of this polymer is several degrees below

body temperature (37 C), which means that it becomes a

soft, sticky material when placed in the body. Because the

polymer is being developed for use as a suture material, it is

undesirable for the polymer to become soft during the

suturing process. Therefore, poly(anhydride-esters) with Tg's

higher than body temperature need to be developed.[128,

129]

Polyamide:- The synthetic aliphatic polyamides are

polymeric compounds frequently referred to as

Nylons which form an important group of poly

condensation polymers. They are linear molecules

(i.e. aliphatic) that are semi-crystalline and

thermoplastic in nature (Kiely et al.,1994; Gaymans

and Sikkema, 1999; Hopf, 2001). A typical

polyamide chain consists of amide groups separated

by alkane segments and the number of carbon atoms

separating the nitrogen atoms which defines the

particular polyamide type. The aliphatic polyamides

are very useful and versatile material that are

9 Advances in Polymer Science and Technology: An International Journal 2012; 2 (1): 1-15

Figure 7. Hydrolytic degradation of poly(anhydride-esters)

Figure 8. General poly (anhydride-ester) structure.

valuable because of their superior physicochemical

and physicomechanical properties such as abrasion

resistance, chemical inertness, relatively high

modulus, minimal degradation, ease of processing,

thermo plasticity, higher melting points and heat

resistance than many other semi-crystalline

polymers such as polyethylene (Makino et al., 1990;

Kiely et al., 1994; Chattaraj et al., 1995; Jones et al.,

1997; Gaymans and Sikkema, 1999; Murthy, 1999;

Ostad and Gard, 2000; Hopf, 2001; Li et al., 2001;

Sikorski et al., 2001; Ostad et al., 2002; Fornes et

al., 2003; Cui and Yan, 2005).

The aforementioned physical properties as well as the

extensive clinical use of the synthetic aliphatic polyamides as

surgical sutures (Van, 1996; Lundborg et al., 1997; Dolorico

et al., 2003; Lee et al., 2003; Seitz et al., 2003; Lai, 2004)

demonstrates their biocompatibility and non-toxicity and

make them attractive for use in the design and development

of drug delivery systems.

Phosphorous based derivatives:-

I). Polyphosphazenes:- It consists of phosphorous atoms

attached to either carbon or oxygen. Polyphosphazenes,

another new class of polymer are being investigated for

delivery of proteins[130]. The uniqueness of this class of

polymer lies in the chemical reactivity of phosphorous which

enables a wide range of side chains to be attached for

manipulating the biodegradation rates and the molecular

weight of polymer.[131].

10 Advances in Polymer Science and Technology: An International Journal 2012; 2 (1): 1-15

Others:-

Polyorthoesters:- Poly(orthoester)s (POE) are another

family of polymers identified as degradable polymers suitable

for orthopaedic applications. Heller and coworkers reported

on the synthesis of a family of polyorthoesters (Figure 6) that

degrades by surface erosion (Ng et al., 1997). With the

addition of lactide segments as part of the polymer structure,

tunable degradation times ranging from 15 to hundreds of

days can be achieved. The degradation of the lactide

segments produces carboxylic acids, which catalyze the

degradation of the orthoester (Ng et al., 1997). Preliminary

in-vivo studies have shown that POE (Figure 6) to increase

bone growth in comparison with poly(dilactide-co-glycolide)

(Andriano et al., 1999).

Conclusion: - Biodegradable polymers have proven their

potential for the development of new, advanced and efficient

drug delivery system. They are capable of delivering a wide

range of bioactive materials. Today the stress is on patient

compliance and to achieve this odjective there is spurt in

development of NDDS. As the herbal excipients are

promising biodegradable materials, these can be chemically

compatible with the excipients in drug delivery systems. In

addition herbal excipients are non-toxic, freely available, and

less expensive compared to their synthetic counterparts. They

have a major role to play in pharmaceutical industry.

Therefore, in the years to come, there is going to be

continued interest in the natural excipients to have better

materials for drug.

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Source of support: Nil; Conflict of interest: None declared