Pan Yan, Li Ying-jian, Zhao Hui-ying, Zheng Jun-min, Xu Hui, Wei Gang, Hao Jin-song, Cui Fu-de
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Int J Pharm. 2002 Dec 5;249(1-2):139-47. doi: 10.1016/s0378-5173(02)00486-6.
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%.
目前有许多正在进行的研究致力于提高肽和蛋白质制剂的口服生物利用度。生物黏附性多糖壳聚糖纳米粒（CS-NPs）似乎能进一步增强它们在肠道的吸收。在本研究中，通过壳聚糖与三聚磷酸阴离子的离子凝胶化反应制备了载胰岛素的CS-NPs。其粒径分布和zeta电位通过光子校正光谱法和激光多普勒风速仪测定。通过监测给予不同剂量载胰岛素CS-NPs口服后四氧嘧啶诱导的糖尿病大鼠的血糖水平，研究了CS-NPs增强胰岛素肠道吸收及提高胰岛素相对药理生物利用度的能力。CS-NPs的粒径在250 - 400 nm范围内，其多分散指数小于0.1，带正电荷，稳定性良好。发现胰岛素的包封率高达80%，其体外释放呈现出具有pH敏感性的较大初始突释。在体内，CS-NPs比壳聚糖水溶液能更大程度地增强胰岛素的肠道吸收。最重要的是，给予CS-NPs中21 I.U./kg胰岛素后，低血糖持续时间超过15小时，相对于皮下注射胰岛素溶液，平均药理生物利用度高达14.9%。
