A novel pH-sensitive hydrogel composed of N.pdfVIP

Journal of Controlled Release 96 2004 285– 300 /locate/jconrel A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery a a b a Sung-Ching Chen , Yung-Chih Wu , Fwu-Long Mi , Yu-Hsin Lin , Lin-Chien Yu a, Hsing-Wen Sunga,* a Department of Chemical Engineering, National Tsing Hua University, 101, Section 2, Kung-Fu Road, Hsinchu 30013, Taiwan, ROC b Division of Applied Chemistry, Department of Applied Science, Chinese Naval Academy, Kaohsiung, Taiwan, ROC Received 29 August 2003; accepted 5 February 2004 Abstract A novel pH-sensitive hydrogel system composed of a water-soluble chitosan derivative N,O-carboxymethyl chitosan, NOCC and alginate blended with genipin was developed for controlling protein drug delivery. Genipin, a naturally occurring cross-linking agent, is significantly less cytotoxic than glutaraldehyde and may provide a less extent of cross-linking to form a semiinterpenetrating polymeric network semi-IPN within the developed hydrogel system. The drug-loading process used in the study was simple and mild. All procedures used were performed in aqueous medium at neutral environment. In the study, preparation of the NOCC/alginate-based hydrogels was reported. Swelling characteristics of these hydrogels as a function of pH values were investigated. Additionally, release profiles of a model protein drug bovine serum albumin, BSA from test hydrogels were studied in simulated gastric and intestinal media. The semi-IPN formation of the genipin-cross-linked NOCC/ alginate hydrogel was confirmed by means of the scanning electron microscopy-energy dispersive X-ray spectrometer SEM- EDS and the ninhydrin assays. The percentage of decrease of free amino groups and cross-linking density for the NOCC/ alginate hydrogel cross-linked with 0.75 mM genipin were 18% and 26 mol/m3, respectively. At pH 1.2, the swelling ratio of the g