Improvement in the in situ gelling properties of deacetylated gellan gum by the immobilization of thiol groups.
The rheological properties of an in situ crosslinking thiolated deacetylated gellan gum were examined in vitro. Mediated by a carbodiimide, L-cysteine was covalently bound to deacetylated gellan gum (DGG). The deacetylated gellan gum-cysteine (DGG-Cys) conjugate displayed 216.53 +/- 59.54 micromol thiol groups per gram polymer (means +/- SD, n = 3). The thiolated polymer was capable of forming inter- and/or intramolecular disulfide bonds in aqueous solution (1.5%; m/m) at pH 7. After 6 h of incubation at room temperature, storage modulus, loss modulus, and complex viscosity increased 300-, 6.4-, and 26.6-fold, respectively, relative to the unthiolated polymer. Loss tangent of DGG-Cys was <1, indicating a gel, whereas the corresponding unmodified polymer had a loss tangent of >1, indicating a fluid. Frequency sweep measurements demonstrated an increase in crosslinking of the thiolated polymer as a function of time. DGG-Cys appeared to be superior to the unmodified polymer also in the presence of physiological cation concentrations found (e.g., in tear fluid and nasal secretion), which is referred to rheological properties. The polymer generated within this study represents a promising novel excipient for various drug delivery systems in which in situ gelling properties are favorable.
Krauland
Alexander H
AH
Institute of Pharmaceutical Technology and Biopharmaceutics, Center of Pharmacy, University of Vienna, Althanstr. 14, A-1090 Vienna, Austria.
Leitner
Verena M
VM
Bernkop-Schnürch
Andreas
A
D000107:Acetylation; D002412:Cations; D002626:Chemistry, Pharmaceutical; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D004337:Drug Carriers; D004339:Drug Compounding; D005782:Gels; D011108:Polymers; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D012212:Rheology; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D002412:Cations; D003432:Cross-Linking Reagents; D004220:Disulfides; D004337:Drug Carriers; D005782:Gels; D011108:Polymers; D011135:Polysaccharides, Bacterial; D013438:Sulfhydryl Compounds; C048288:gellan gum; D003545:Cysteine