5β-Cholanic Acid/Glycol Chitosan Self-Assembled Nanoparticles (5β-CHA/GC-NPs) for Enhancing the Absorption of FDs and Insulin by Rat Intestinal Membranes
5β-Cholanic Acid/Glycol Chitosan Self-Assembled Nanoparticles (5β-CHA/GC-NPs) for Enhancing the Absorption of FDs and Insulin by Rat Intestinal Membranes
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DOI：
10.1208/s12249-018-1242-6
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发表时间：
2019-01
影响因子：
3.3
通讯作者：
Chengyun Yan;Jiwei Gu;Y. Lv;Weiguo Shi;Zhan Huang;Ying Liao
中科院分区：
文献类型：
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作者：
Chengyun Yan;Jiwei Gu;Y. Lv;Weiguo Shi;Zhan Huang;Ying Liao
采用原位闭环法研究了5β-胆酸纳米粒修饰的乙二醇壳聚糖(5β-CHA/GC-NPs)对一种肠道吸收较差的药物的促吸收作用。我们选择了荧光素、异硫氰酸酯标记的右旋糖苷(FDs)和胰岛素作为模型药物。采用透析法制备了5种不同药物负载的β-CHA/GC-NPs，并对其理化性质和体外释药特性进行了评价。结果表明，5种β-CHA/GC-NPs显著增加胰岛素和FDs在空肠、回肠和结肠的吸收。所有药物在空肠的吸收率均高于回肠和结肠。此外，5种β-CHA/GC-NPs对FDs从空肠吸收的促进作用随分子量的增加而减弱。在毒性试验中，5种β-CHA/GC-NPs没有显著增加蛋白质的释放和乳酸脱氢酶的活性，说明纳米粒没有对肠道造成任何膜损伤。这些结果表明，5β-CHA/GC-NPs是安全有效的促进药物吸收的载体，但其肠道吸收能力较差。
The absorption-enhancing effects of glycol chitosan modified by 5β-cholanic acid nanoparticles (5β-CHA/GC-NPs) on a drug with poor absorption in the intestine were studied by the method of in situ closed loop. We chose fluorescein isothiocyanate-labeled dextrans (FDs) and insulin as the model drugs. 5β-CHA/GC-NPs loaded to different drugs were prepared by the dialysis method, and the physicochemical characteristics and in vitro release profiles of nanoparticles were also estimated. The results showed that 5β-CHA/GC-NPs markedly increased the absorption of insulin and FDs in the jejunum, ileum, and colon. The ratios of absorption for all the drugs in the jejunum were higher than those in the ileum and colon. In addition, the enhancing effect of 5β-CHA/GC-NPs for the absorption of FDs from the jejunum was decreased with increasing molecular weights. In the toxicity test, 5β-CHA/GC-NPs did not significantly increase the release of protein and the activities of LDH, indicating that the nanoparticles did not cause any membrane damage to the intestine. These findings suggested that 5β-CHA/GC-NPs were safe and useful carriers for enhancing the absorption of the drug with poor absorption by intestinal membranes.