POLYELECTROLYTES: AS A DRUG DELIVERY SYSTEM

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CHITOSAN BASED POLYELECTROLYTE COMPLEXES

Introduction:
Chitosan refers to a series of polymers that are deacetylated derivatives of the natural polysaccharide, chitin, with different degrees of deacetylation and molecular weights. It is composed of β-1,4-linked glucosamine (deacetylated units) and N-acetyl-d-glusoamine (acetylated units) (Figure 1) with typical degrees of deacetylation between 70 and 95% and molecular weights between 10 and 1,000 kDa . Highly refined grades of chitosan have been used in pharmaceutical formulations as a release-controlling agent in oral preparations.

Figure 1: Chitosan consisting of N-acetyl-d-glucosamine and glucosamine units.

Polyelectrolyte Complexes between Chitosan and Natural Polymers:

Chitosan-alginate polyelectrolyte complex:
The negatively charged carboxylic acid  groups of manuronic and guluronic acid units in alginate interact electrostatically with the positively charged amino groups of chitosan to form a polyelectrolyte complex. Alginate is one of the most studied anionic polyelectrolytes in complexation with chitosan polyelectrolyte because the complex formed between these two polymers is still biodegradable and biocompatible but mechanically stronger at lower pH values where chitosan dissolve.

Figure 2: Chemical structure of alginate

Chitosan-carrageenan polyelectrolyte complex:
Carrageenan is the generic name for a family of high molecular weight sulphated polysaccharides obtained from certain species of red seaweeds. There are three basic types of carrageenan, namely kappa (κ), iota (ι) and lambda (λ) carrageenan (Figure 3). It was shown that the nature or type of carrageenan considerably influence the characteristics of the polyelectrolyte complex that is formed with chitosan. The mechanical strength of polyelectrolyte complex gels formed between chitosan and different carrageenans were in the order λ- > ι- > κ-carrageenan. and although the latter two formed stronger gels due to the formation of more cross-links as a result of their double helix secondary structures, these gels were also more brittle.

Figure 3: Chemical structures of (a) λ-carrageenan, (b) ι-carrageenan and (c) κ-carrageenan

Chitosan-pectin polyelectrolyte complex:
The polysaccharides of the plant cell wall consist mainly of cellulose, hemicelluloses and pectin. Pectin is a linear polysaccharide composed of α-1,4-linked D-galacturonic acid units, however, this linear structure is interrupted with highly branched regions in the polymer chain (Figure 4). The composition of the pectin molecule varies from source to source, e.g. pectin from citrus fruit contains less neutral sugars and has a smaller molecular size than pectin from apples.[2]

Figure 4: Chemical structure of pectin.

Chitosan-xanthan gum polyelectrolyte complex:
Xanthan gum is an exopolysaccharide secreted from Xanthomonas campestris. It consists of a cellulosic backbone, namely β-(1,4)-d-glucopyranose glucan, with a trisaccharide side chain, namely (3,1)-α-d-mannopyranose-(2,1)-β-d-glucuronic acid-(4,1)-β-d-mannopyranose, on every second glucose residue (Figure 5).

Figure 5: Chemical structure of xanthan gum

Chitosan-hyaluronic acid polyelectrolyte complex:
β (1,3)-N-acetyl-d-glucosamine and α (1,4)-d-glucuronic acid repeating units linked by β (1→3) bonds (Figure 6). It was shown that the polyelectrolyte complex between chitosan and hyaluronic acid protected hyaluronic acid against enzymatic hydrolysis, but only at pH values different from the optimal pH of the enzyme. The results from this study revealed that the chitosan-hyaluronic acid polyelectrolyte complex unfortunately had less cell proliferation and wound healing effects compared to chitosan alone.

Figure 6: Chemical structure of hyaluronic acid

Chitosan-gelatine polyelectrolyte complex:
Gelatine is a heterogeneous mixture of protein fractions consisting of single or multi-stranded polypeptides (Figure 7). It is obtained by partial hydrolysis of animal collagen derived from skin, white connective tissues and bones. It was shown that the polyelectrolyte complex between chitosan and gelatine can only occur at a pH value above 4.7 (which represents the isoelectric point of gelatin and above this value the net charge on gelatine type B is negative) and below 6.2 (above which chitosan start to precipitate out of solution).Chitosan-gelatine polyelectrolyte complex sponges containing tramadol hydrochloride.

Figure 7: Typical structure of gelatin

Polyelectrolyte Complexes between Chitosan and Synthetic Polymers:
Chitosan-cross-linked-poly(acrylic acid) polyelectrolyte complexes:
Polycarbophil (Noveon AA-1®) and Carbopol are high molecular weight polymers consisting of acrylic acid monomers. The poly (acrylic acid) chains are cross-linked with divinyl glycol to form polycarbophil and polyalkenyl alcohols such as allyl ethers of pentaerythritol or allyl ethers of sucrose to form Carbopol. Cross-linking of the poly (acrylic acid) chains with divinyl glycol in the case of polycarbophil renders only 20% of the carboxylic acid groups inaccessible for interactions with other compounds.[2]

Chitosan-polymethacrylate copolymer (Eudragit) polyelectrolyte complexes:
Polyelectrolyte complexes formed between chitosan with different molecular weights and Eudragit L100 or Eudragit L100-55 were compressed into matrix type tablets containing diclofenac sodium as model drug. Different aspects of the complex systems were investigated such as the molar ratio, structure, swelling and drug release profiles. Results indicated that this polyelectrolyte complex has high potential for manufacture of controlled release drug delivery systems. Factors such as the composition of the polyelectrolyte complex in terms of polymer ratios, Eudragit type and molecular weight of the chitosan influenced the drug release rate from the matrix type tablets.

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