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Chen SC, Wu YC, Mi FL, et al. A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery. J Control Release. 2004;96(2):285-300doi: 10.1016/j.jconrel.2004.02.002.
Chen, S. C., Wu, Y. C., Mi, F. L., Lin, Y. H., Yu, L. C., & Sung, H. W. (2004). 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, 96(2), 285-300. https://doi.org/10.1016/j.jconrel.2004.02.002
Chen, Sung-Ching, et al. "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 vol. 96,2 (2004): 285-300. doi: https://doi.org/10.1016/j.jconrel.2004.02.002
Chen SC, Wu YC, Mi FL, Lin YH, Yu LC, Sung HW. A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery. J Control Release. 2004 Apr 28;96(2):285-300. doi: 10.1016/j.jconrel.2004.02.002. PMID: 15081219.
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J Control Release. 2004 Apr 28;96(2):285-300. 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

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

Affiliations

  1. Department of Chemical Engineering, National Tsing Hua University, 101 Section 2, Kung-Fu Road, Hsinchu 30013, Taiwan, ROC.

PMID: 15081219 DOI: 10.1016/j.jconrel.2004.02.002

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/m(3), 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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