Synthesis and characterisation of mucoadhesive thiolated polymers.

7. Davide Guggi, Andreas Bernkop-Schnurch Matrix tablets based on thiolated poly(acrylic acid) / International Journal of Pharmaceutics 274 (2004) 97-105. 8. A. Bernkop-Schnu¨ rch, in: S. Dumitriu (Ed.), Mucoadhesive Polymers, Polymeric Biomaterials, Marcel Dekker, New York, 2000, pp. 147– 165

Synthesis and Characterization of Novel Bioadhesive Material Thiolated Chitosan[J].

b) Thiolated Mucoadhesive Polymers: These are thiomers which are derived from hydrophilic polymers such as polyacrylates, chitosan or deacetylated gallan gum. The presence of the thiol group increases the residence time by promoting covalent bonds with the cystiene residues in mucus. The disulphide bonds may also alter the mechanism of drug release from the delivery system due to increased rigidity and cross linking 53. Improved mucoadhesive properties of the thiolated polymers:

Synthesis and Characterization of pH Tolerant and Mucoadhesive ..

Thiolated polymers: Synthesis and in vitro evaluation of polymer‑cysteamine conjugates.

The synthesis of S-protected thiolated chitosan is a tow-step procedure. The first modification involved the covalent attachment of thioglycolic acid (TGA) to chitosan (CS) due to the formation of amide bonds between the primary amino groups of the polymer and carboxylic acid groups of TGA as described previously (). For the second modification, the aromatic ligands 6-mercaptonicotinamide (6-MNA) as well as its dimer 6,6′-dithionicotinamide (6,6-DTNA), which are commercially not available, had to be synthesized according a method developed by . The second modification step was then achieved by disulfide bond formation between free thiol groups of the thiolated chitosan and the aromatic ligand ().

Improved mucoadhesive property of thiolated pectin over the ..

Mucoadhesive properties of the S-protected thiolated chitosans were on the one hand tested by rotating cylinder method. This method is supposed to simulate an in vivo situation, as it imitates the adhesion and cohesiveness of the polymer in physiological medium. Unmodified chitosan tablets detached from the intestinal mucosa or solved within 10 h, while thiolated and S-protected tablets remained attached for at least 32 h (CS-TGA-340) and 50 h (TGA-MNA-340) demonstrating at least 3.2- and 5-fold improved mucoadhesive properties. This effect was more pronounced for MNA-660 tablets, which were adhesive on the mucosa for at least 90 h, resulting in a 2-fold improvement compared to their corresponding thiomer tablets (CS-TGA-660) and 9-fold to unmodified chitosan tablets. Compared with previous studies, chitosan-4-butylamidine for example with 240 μmol/g thiol groups remained on the mucosa for more than 161 h (). In this study, however, the fully immersed cylinder was agitated with 125 rpm only, whereas the rotational speed in the present study was set to 200 rpm and the experiment was stopped after 120 h. Nevertheless, neither the highest thiolated tablet (CS-TGA-980) nor the corresponding S-protected tablet (TGA-MNA-980) were detached after this period, demonstrating the effectiveness of this class of thiomers and placing them among the most mucoadhesive polymers to our notice (). Outcomes of this study are shown in .

| International journal of pharmaceutics | 4/30/2016

Swelling behavior of matrix tablets has a great impact on their adhesive and cohesive properties, drug release and stability. Results revealed that tablets of unmodified CS swelled more rapid in the beginning than thiolated and S-protected ones, because of their stronger hydrophilic character and higher number of charges on the polymer. After 2 h, a gradual decrease in the tablet weight of unmodified CS was observed related to a slow erosion process within the following hours of the experiment. This observation might be explained by the low cohesiveness of CS tablets and the impossibility of cross-linking within the polymer backbone. Furthermore, results demonstrated that the covalent attachment of TGA to CS has a significant influence (p ). However, due to this cross-linking process, tablets can absorb water in quantities which are multiples of their own weight and can fixate them firmly within their polymer networks. In contrast, the incorporation of an aromatic ligand on the thiomer backbone reduced the swelling behavior of all S-protected tablets. TGA-MNA-980 tablets, for instance, gained a maximum weight of 105 mg after 12 h incubation, which is more than 40% lower than that of CS-TGA-980 tablets. In addition, it could be shown that water uptake for all S-protected tablets depends on the amount of covalently attached 6-MNA and remaining free thiol groups. Due to a pronounced hydrophobic character, it took longer until water could penetrate inside the tablet and intramolecular disulfide bond formation of remaining free thiol groups took place. Consequently, the amount of covalently attached aromatic ligand as well as remaining free thiol groups on the S-protected tablet are responsible for a slower swelling in the beginning following an increased water uptake once water began to penetrate into the tablet. Nevertheless, pointed out that a low swelling behavior can be advantageous for prolonged mucoadhesion. Mucoadhesive materials need to take up water from the underlying mucosal tissues by absorbing, swelling and capillary effects leading to a considerably stronger adhesion. However, excessive water uptake will lead to overhydration forming slippery mucilage and result in less adhesiveness (). Hence, the slow swelling of S-protected thiomers might be advantageous to avoid overmuch hydration and loss of adhesiveness. Results of the water uptake studies are presented in (a).