Evaluation of in vitro enzymatic degradation of various thiomers and cross-linked thiomers.
The aim of this study was to examine the biodegradability of thiomers and cross-linked thiomers in comparison with unmodified polymers. Disulfide-cross-linked conjugates were prepared by air oxidation at room temperature. Thiomers were investigated by viscosity measurements and spectrophotometric assays. The influence of different factors on the hydrolysis rate, such as the degree of modification of thiomers, structure of the conjugates, pH value of the reaction medium, and the impact of the process of cross-linking were evaluated. Due to the modification, thiolated chitosans degraded 12.9-24.7% less than unmodified chitosan in the framework of viscosity measurements. In addition, the hydrolysis degree of thiolated alginates and modified carboxymethylcelluloses was 25.6-32.4% and 18.4-27.0% lower, respectively, in comparison to the corresponding unmodified polymers. Conjugates with higher coupling rate of thiol groups were degraded even more slowly. Moreover, the cross-linking process via disulfide bonds additionally reduced the rate of thiomer degradation. The range of degradation rates achieved in vitro could be modified by alterations of the contents of thiol and disulfide groups, as well as by suitable design of the polymer structure and ligands used. These results represent helpful basic information for the development of mucoadhesive drug delivery systems, implantable delivery systems and tissue engineering constructs.
Kafedjiiski
Krum
K
Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Innsbruck, Austria.
Föger
Florian
F
Hoyer
Herbert
H
Bernkop-Schnürch
Andreas
A
Werle
Martin
M
D000464:Alginates / Q000737:chemistry / Q000378:metabolism; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002480:Cellulase / Q000737:chemistry / Q000378:metabolism; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000378:metabolism*; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism*; D005978:Glutathione / Q000138:chemical synthesis / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D015394:Molecular Structure; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D011133:Polysaccharide-Lyases / Q000737:chemistry / Q000378:metabolism; D011489:Protein Denaturation; D015203:Reproducibility of Results; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism*; D013678:Technology, Pharmaceutical / Q000379:methods; D014783:Viscosity
D000464:Alginates; D003432:Cross-Linking Reagents; D004220:Disulfides; D004798:Enzymes; D011108:Polymers; D013438:Sulfhydryl Compounds; D048271:Chitosan; D009113:Muramidase; D002480:Cellulase; D011133:Polysaccharide-Lyases; C016158:poly(beta-D-mannuronate) lyase; D005978:Glutathione; D002266:Carboxymethylcellulose Sodium