title: In situ gelling properties of chitosan-thioglycolic acid conjugate in the presence of oxidizing agents.
abstract: The rheological behaviour of chitosan-thioglycolic acid conjugate (chitosan-TGA) in the presence of four oxidizing agents was investigated. Chitosan-TGA was synthesized via amide bond formation between the primary amino group of chitosan and the carboxylic acid group of thioglycolic acid. The sol-gel phase transition of the polymer was determined by rheological measurements. Moreover, cytotoxicity of the gel in combination with each oxidizing agent was evaluated utilizing LDH and MTT assay. The modified chitosan displayed 1053+/-44 micromol/g thiol groups. Results of rheological studies showed that 1% (m/v) chitosan-TGA without any oxidizing agents became gel within 40 min. In contrast, when the oxidizing agents hydrogen peroxide, sodium periodate, ammonium persulfate and sodium hypochlorite were added, respectively, gelation took place within a few minutes. Within 20 min, hydrogen peroxide having been added in a final concentration of 25.2 nmol/L increased dynamic viscosity of 1% (m/v) chitosan-TGA up to 16,500-fold. This can be explained by the formation of inter- and/or intramolecular disulfide bonds which were indirectly verified via the decrease in thiol groups. Additionally, evidence of an increase in cross-linking of thiolated chitosan as a function of time was provided by frequency sweep measurements. Furthermore, viability of Caco-2 cells having been incubated with chitosan-TGA/oxidizing agent systems assessed by MTT assay was 70-85% and the percentage of LDH release was only in case of the chitosan-TGA/ammonium persulfate system significantly (p<0.05) raising compared to the negative control. According to these results, chitosan-TGA/oxidizing agent combinations might be a promising novel in situ gelling system for various pharmaceutical applications such as a controlled drug release carrier or for tissue engineering.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 52, Josef Möller Haus, A-6020 Innsbruck, Austria.
authors.forename: Duangkamon
authors.initials: D
authors.lastname: Sakloetsakun
authors.forename: Juliane M R
authors.initials: JM
authors.lastname: Hombach
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry* / Q000494:pharmacology; D005782:Gels / Q000737:chemistry*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D013864:Thioglycolates / Q000737:chemistry* / Q000494:pharmacology; D014783:Viscosity
chemical_list: D005782:Gels; D011108:Polymers; D013864:Thioglycolates; D048271:Chitosan; D007770:L-Lactate Dehydrogenase