Mucoadhesive polymers anionic

The periodontal pocket is another site for drug delivery in the oral cavity. Needleman et al. [46] investigated three mucoadhesive polymers (cationic chitosan, anionic xanthan gum, neutral polyethylene oxide) in vitro, using organ cultures, and in vivo in patients on their periodontal and oral mucosa. Of the polymers studied, chitosan displayed the longest adhesion in vitro and on the periodontal pockets, and the shortest adhesion on oral mucosa. 

Bernkop-Schniirch, A. and Gilge, B. Anionic mucoadhesive polymers as auxiliary agents for the peroral administration of (poly)peptide drugs influence of the gastric juice. Drug Dev. Ind. Pharm. 2000 26, 2, 107-113. 

Thiolated polymers, also termed thiomers, are conventional mucoadhesive polymers chemically modified to contain a cysteine residue in the polymer chain and thus establish covalent disulfide bonds with mucin." They can be manufactured to be either cationic (mostly thiolated chitosans) or anionic (carboxylic acid-containing polymers) however, their mucoadhesive extent will mostly be determined by their capacity to covalently bind to mucin. The polypeptide backbone of mucin can be divided into three major subunits tandem repeat array, carboxyl-, and amino-terminal domains. While the amino-terminal domain contains some of the cysteine residues, the carboxyl-terminal domain contains more than 10% of the cysteine residues. These cysteine-rich regions are responsible for forming the large mucin oligomers and ultimately, the groups that allow for the covalent mucoadhesive bond formation with oral mucosal systems." ... 

Contrary to what has been reported for non-covalently binding mucoadhesive polymers, the disulfide bond is not influenced by ionic strength, electrostatic, or hydrophobic domain interactions." The extent of the disulfide bond is strictly related to the concentration of thiolate anions, which is the group that will go through thiol/disulfide exchange reactions and oxidation processes. The concentration of the thiolate groups is mostly determined by the p T value of the thiol group. 

Poly(acrylic acid) (PAA) (Figure 16.5) is an anionic mucoadhesive polymer produced by the radical polymerization of acrylic add. PAA and its derivatives—weakly crosslinked PAAs, also known as Carbomers or Carbopol—are widely used in ophthalmic formulation, such as the ones used for the management of the dry eye condition. Generally, PAA and its derivatives are used in the preparation of mucoadhesive ocular drug delivery formulations [25], either in the form of viscous gels [26], nanoparticles... 

The mucoadhesive properties of several classes of hydrogels have been identified, and two types of polymers have attracted special attention. Polyacrylates and their cross-linked modifications represent the anionic type, chitosan and its derivatives the cationic group. In addition, both types of polymers show a number of interesting characteristics beneficial for the administration of a wide range of therapeutics. 

For bioadhesive applications, anionic polymers appear to provide the most effective balance between adhesiveness and toxicity, with carboxylic materials preferred over sulfonic polymers [400]. Polyfacrylic acid) microparticles have been identified as particularly effective bioadhesive materials [402]. Studies with poly(acrylic acid) microparticles have indicated that, while water-swollen particles exhibit good bioadhesion, dry polymer particles give no adhesion at all. In addition, adhesive strength increases as the degree of ionization of the polymer is increased [402]. Thus the expanded nature of the polymer network is important to mucoadhesion, probably via polymer interdiffusion and entanglement with mucin [403],... 

Langoth et al. [86] studied the properties of matrix-based tablets containing the novel pentapeptide leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) that has been shown to have pain-modulating properties. The matrix-based tablets were made with the thiolated polymer PCP. The covalent attachment of cysteine to the anionic polymer PCP leads to an improvement of the stability of matrix tablets, enhances the mucoadhesive properties, and increases the inhibitory potency of PCP towards buccal enzymes. All these factors lead to stability of the peptide and a controlled drug release for the peptide was obtained for more than 24 h. Also, the tablets based on thiolated PCP remained attached on freshly excised porcine mucosa 1.8 times longer than the corresponding unmodified polymer. 

However, according to Park and Robinson [193], poly anions are better than polycations in terms of binding and potential toxicity. In general, both anionic and cationic charged polymers demonstrate better mucoadhesive properties than nonionic polymer, such as cellulose derivates or PVA [194,195],... 

Leung, S.H. Robinson, J.R. The contribution of anionic polymer structural features to mucoadhesion. J. Controlled Release 1988, 5, 223-231. 

Anionic polymeric permeation enhancers have a different effect. They do not interact directly with the membrane, but bind and deplete Ca ions from the extracellular cell medium, which leads to an opening of the tight junctions [111]. The properties of anionic polymers have also been improved. By immobilization of free sulf-hydryl groups onto various polymers, their permeation-enhancing effect on hydrophilic compounds is strongly increased [112]. In addition, thiolated polymers (thiomers) show improved mucoadhesive properties which allows them to concentrate in the area of drug absorption [113]. 

A general conclusion that can be drawn from Table 51.3 is that charged polymers both anionic and cationic demonstrate a better mucoadhesive capacity in comparison to non-ionic cellulose-ethers or polyvinyl alcohol (PVA). 

Many PECs are prepared using chitosan as the polycationic component, therefore they will be discussed separately. Chitosan, the product of N-deacetylation of chitin, is one of the most commonly used cationic polymers of pharmaceutical interest due to its biocompatibility, nontoxicity, and mucoadhesivity. It is frequently used to form PECs, often in combination with alginate, carrageenan," hyaluronic acid, chondroitin sulfate (CS)," carboxymethyl cellulose (CMC), or poly(galacturonic acid), since these are natural anionic polysaccharides with favorable pharmaceutical properties. 

Poly(acrylic acid)-cysteine and chitosan-4-thiobulylamidine were evaluated as anionic and cationic polymers for the preparation of a DDS for riboflavin-S -monophosphate sodium salt dihydrate as a model drug. The particles had a mean diameter of 336.5 16.5 and 396.3 17.0 nm and a zeta potential of - 20.0 1.0 and -I- 27.2 0.5 mV, respectively. It was found that glutathione in combination with thiomers has a significant influence for increasing permeation, and that thiolated particles of both anionic and cationic polymers had improved mucoadhesive and controlled release properties. Therefore, they can be potentially applied as gastroretentive delivery systems. ... 

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