Kofuji Kyoko, Akamine Hiroyuki, Oshirabe Hitomi, Maeda Yasuyo, Murata Yoshifumi, Kawashima Susumu
Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa 920-1181, Japan.
J Biomater Sci Polym Ed. 2003;14(11):1243-53. doi: 10.1163/156856203322553464.
Chitosan (CS) gel beads were prepared in a 10% (w/v) aqueous amino acid solution (pH 9.0) as a vehicle for delivering peptide and protein drugs. CS gel beads with a weight-average molecular weight of (16-280) x 10(4) were employed in this study. Preparation of the CS gel beads was affected by properties such as molecular weight and degree of deacetylation. Insulin, which is commonly used to assess protein drug delivery, was retained in the CS gel beads. Drug release from the CS gel beads was governed by diffusion of drug from the gel matrix. Sustained release of insulin from the CS gel beads was observed, despite the fact that insulin is a comparatively water-soluble drug. because insulin formed a complex with CS. Modification of the CS gel matrix by chondroitin sulfate inhibited release of insulin from the gel beads. CS gel beads were implanted into air pouches prepared subcutaneously on the dorsal surface of diabetic mice in order to investigate the efficacy of insulin retained in the CS beads. Blood glucose levels were found to be reduced after implantation of CS gel beads retaining insulin. CS gel beads may possibly improve the stability and control of insulin release. These observations indicate that CS beads are a promising biocompatible and biodegradable vehicle for peptide and protein delivery.
壳聚糖（CS）凝胶珠是在10%（w/v）氨基酸水溶液（pH 9.0）中制备的，作为递送肽和蛋白质药物的载体。本研究采用重均分子量为（16 - 280）×10⁴的CS凝胶珠。CS凝胶珠的制备受分子量和脱乙酰度等性质的影响。常用于评估蛋白质药物递送的胰岛素被保留在CS凝胶珠中。CS凝胶珠中的药物释放受药物从凝胶基质扩散的控制。尽管胰岛素是一种相对水溶性的药物，但仍观察到胰岛素从CS凝胶珠中的持续释放，因为胰岛素与CS形成了复合物。硫酸软骨素对CS凝胶基质的修饰抑制了胰岛素从凝胶珠中的释放。为了研究保留在CS珠中的胰岛素的疗效，将CS凝胶珠植入糖尿病小鼠背部皮下制备的气袋中。发现植入保留胰岛素的CS凝胶珠后血糖水平降低。CS凝胶珠可能会提高胰岛素释放的稳定性和可控性。这些观察结果表明，CS珠是一种用于肽和蛋白质递送的有前景的生物相容性和可生物降解的载体。
