[논문]A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery

Chen, Sung-Ching; Wu, Yung-Chih; Mi, Fwu-Long; Lin, Yu-Hsin; Yu, Lin-Chien; Sung, Hsing-Wen

doi:10.1016/j.jconrel.2004.02.002

A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery

Journal of controlled release : official journal of the Controlled Release Society, v.96 no.2, 2004년, pp.285 - 300

Chen, Sung-Ching (Department of Chemical Engineering, National Tsing Hua University, 101, Section 2, Kung-Fu Road, Hsinchu 30013, Taiwan, ROC) , Wu, Yung-Chih (Department of Chemical Engineering, National Tsing Hua University, 101, Section 2, Kung-Fu Road, Hsinchu 30013, Taiwan, ROC) , Mi, Fwu-Long (Division of Applied Chemistry, Department of Applied Science, Chinese Naval Academy, Kaohsiung, Taiwan, ROC) , Lin, Yu-Hsin (Department of Chemical Engineering, National Tsing Hua University, 101, Section 2, Kung-Fu Road, Hsinchu 30013, Taiwan, ROC) , Yu, Lin-Chien (Department of Chemical Engineering, National Tsing Hua University, 101, Section 2, Kung-Fu Road, Hsinchu 30013, Taiwan, ROC) , Sung, Hsing-Wen (Corresponding author. Tel.: +886-3-574-2504)

Abstract ▼ AI-Helper

AbstractA 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 genipin-cross-linked NOCC/alginate hydrogel was limited (2.5) due to formation of hydrogen bonds between NOCC and alginate. At pH 7.4, the carboxylic acid groups on the genipin-cross-linked NOCC/alginate hydrogel became progressively ionized. In this case, the hydrogel swelled more significantly (6.5) due to a large swelling force created by the electrostatic repulsion between the ionized acid groups. The amount of BSA released at pH 1.2 was relatively low (20%), while that released at pH 7.4 increased significantly (80%). The results clearly suggested that the genipin-cross-linked NOCC/alginate hydrogel could be a suitable polymeric carrier for site-specific protein drug delivery in the intestine.

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A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery

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