Thiolated chitosan micelles: Highly mucoadhesive drug carriers

Abstract

Current study was aimed to generate thiolated chitosan micelles based on amphiphilic chitosan-stearic acid conjugate (CSA) and to evaluate adhesive properties on mucosal membranes. Chitosan-stearic acid-thioglycolic acid (CSA-TGA) conjugate was synthesized via stearic acid linkage to chitosan and later, thioglycolic acid was covalently attached to CSA. CSA-TGA and CSA were characterized by degree of amine substitution, thiol group determination, ATR-FTIR and cytotoxicity analysis. Micelle size was 13.40±9.38 and 26.30±26.86nm and zeta potential -0.01 and 0.03mV for CSA and CSA-TGA, respectively. In porcine mucus CSA-TGA micelles exhibited 1.80-, 2.12- and 1.72-fold increase in dynamic viscosity, elastic modulus and viscous modulus, respectively. Compared to CSA micelles CSA-TGA micelles remained up to 56.1- fold and 28.6- fold higher degree attached on intestinal and vaginal mucosa, respectively. Taking possibility to incorporate both lipophilic and hydrophilic drugs into these micelles into account, thiol functionalized micelles could be promising carriers for mucosal drug delivery.

Keywords: Amphiphiles; Chitosan; Intestinal mucosa; Mucoadhesion; Polymeric micelles; Vaginal mucosa.