Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo
Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo
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DOI：
10.1016/s0378-5173(02)00486-6
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发表时间：
2002-12-05
影响因子：
5.8
通讯作者：
Cui, FD
中科院分区：
文献类型：
--
作者：
Pan, Y;Li, YJ;Cui, FD
有许多正在进行的研究，以提高肽和蛋白质制剂的口服生物利用度。生物粘附性多糖壳聚糖纳米颗粒（CS-NPs）似乎进一步增强了它们的肠道吸收。在这项研究中，胰岛素负载的CS-NPs通过CS与三聚磷酸盐阴离子的离子凝胶化制备。用光子校正光谱法和激光多普勒测速仪测定了其粒径分布和zeta电位。通过监测口服施用不同剂量的负载胰岛素的CS-NP后四氧嘧啶诱导的糖尿病大鼠的血糖水平，研究CS-NP增强胰岛素的肠吸收和增加胰岛素的相对药理学生物利用度的能力。CS-NP具有在250-400 nm范围内的粒度，并且其多分散指数小于0.1，带正电荷，稳定。发现胰岛素缔合高达80%，并且其体外释放显示出具有pH敏感性的巨大初始突释。CS-NPs在体内比CS水溶液更大程度地增强胰岛素的肠吸收。总之，在施用21 I.U./ kg胰岛素的CS-NP，低血糖延长超过15小时，相对于SC注射胰岛素溶液的平均药理学生物利用度高达14.9%。(C)2002 Elsevier Science B. V.保留所有权利。
There are many ongoing investigations to improve the oral bioavailability of peptide and protein formulations. Bioadhesive polysaccharide chitosan nanoparticles (CS-NPs) would seem to further enhance intestinal absorption of them. In this study, Insulin-loaded CS-NPs were prepared by ionotropic gelation of CS with tripolyphosphate anions. Its particle size distribution and zeta potential were determined by photon correction spectroscopy and laser Dopper anemometry. The ability of CS-NPs to enhance intestinal absorption of insulin and increase the relative pharmacological bioavailability of insulin was investigated by monitoring the plasma glucose level of alloxan-induced diabetic rats after oral administration of various doses of insulin-loaded CS-NPs. CS-NPs had a particle size in the range of 250-400 nm and its polydispersity index was smaller than 0.1, positively charged, stable. Insulin association was found up to 80% and its in vitro release showed a great initial burst with a pH-sensitivity property. CS-NPs enhanced the intestinal absorption of insulin to a greater extent than the aqueous solution of CS in vivo. Above all, after administration of 21 I.U./kg insulin in the CS-NPs, the hypoglycemia was prolonged over 15 h and the average pharmacological bioavailability relative to SC injection of insulin solution was up to 14.9%. (C) 2002 Elsevier Science B.V. All rights reserved.