Preparation of 4-carboxybenzenesulfonamide modified chitosan for delivery of acetazolamide

Abstract

The objective of this research is to modify chitosan (CS) with various ratio of 4-carboxybenzensulfonamide (4-CBS) to improve a mucoadhesive property and thus increases the chance of carbonic anhydrase inhibitor being delivered through the mucosa of the stomach for eradication of H. pylori. The 4-CBS-CSs were characterized by 1H-NMR, FT-IR spectroscopy, DSC and TGA analysis. The 4-CBS-CS (1:0.05) has mucoadhesive property and swelling ratio better than CS, and can tolerate in the stomach condition for at least 24 hours in the simulated gastric fluid (pH 1.2) and the phosphate buffer (pH 5.5). The 4-CBS-CSs were non-toxic to Vero cell and inactive against anti-cancer cell lines of epidermoid carcinoma of oral cavity (KB), breast adenocarcinoma (MCF-7) and small cell lung carcinoma (NCI-H187). Moreover, the 4-CBS-CSs can inhibit Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus) better than CS. The application of 4-CBS-CS is focused on the immobilization of acetozalamide (ACZ) onto CS and the 1:0.05 4-CBS-CS in the form of microspheres by electrospray technique. The particle sizes were in the range of 2-8 𝜇m. The percent of ACZ encapsulation efficiency (%EE) of ACZ-4-CBS-CS (1:1) was 98% (47% for 1:1 ACZ-CS microspheres). In vitro release profiles of acetazolamide in the SGF showed that 4-CBS-CS can prolong release up to 4 hours.