Synthesis of oleoyl-4-carboxybenzenesulfonamide-quaternized chitosan

Abstract

The objectives of this research were to increase mucoadhesive properties of chitosan and then evaluate for using as mucoadhesive drug carrier. Two mucoadhesive modified chitosans, oleoyl-4-carboxybenzenesulfonamide-N-trimethyl chitosan chloride (OA-4-CBS-TMC), and oleoyl-4-carboxybenzenesulfonamide-chitosan N-(3-chloro-2-hydroxy-propyl) trimethylammonium chloride (OA-4-CBS-CS Quat-188), can be achieved by modification of chitosan with 4-CBS and OA conjugated with TMC or CS Quat-188 using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) as a coupling agent. The degree of quaternization (%DQ) of TMC and CS Qaut-188 were 18.90% and 24.05%, respectively. The degree of substitution (%DS) of 4-CBS on TMC, 4-CBS on CS Quat-188, OA on 4-CBS-TMC, and OA on 4-CBS-CS Quat-188 were 9.70%, 10.36%, 34.15%, and 37.88%, respectively which calculated by 1H NMR. Periodic Acid Schiff (PAS) colorimetric method was used to study mucin-conjugated polymer bioadhesive strength in the simulated gastrointestinal fluid (pH 1.2 and 6.4). The OA-4-CBS-TMC and OA-4-CBS-CS Quat-188 showed stronger mucoadhesive properties 2.60, 3.05, 1.48, and 1.80-fold than that of unmodified chitosan at pH 1.2 and at pH 6.4, respectively. An easy and stable one step was presented to fabricate self-assembled well-ordered OA-4-CBS-TMC and OA-4-CBS-CS Quat-188 nanofractal hyperbranch. Nanofractal hyperbranch was prepared by only re-dispersing the polymeric compound in distilled water at a concentration of 2.3 mg/mL. The self-assembled nanofractal hyperbranch had diameter in the range of 2-9 µm with a narrow width distribution. Therefore, both OA-4-CBS-TMC and OA-4-CBS-CS Quat-188 could be suitable to use in gastrointestinal tract.