Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin.
Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin.
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DOI：
10.1016/j.ejpb.2010.09.016
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Yueling Zhang;Wei Wei-Wei;Piping Lv;Lianyan Wang;G. Ma
中科院分区：
文献类型：
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作者：
Yueling Zhang;Wei Wei-Wei;Piping Lv;Lianyan Wang;G. Ma
采用膜乳化技术，结合离子（Ca2+）和聚合物（壳聚糖）固化制备了粒径分布较窄的海藻酸盐-壳聚糖微球。对制备过程进行了观察，并对微球的物理性质（粒径分布、表面形貌、壳聚糖分布、zeta电位）进行了表征。随后，利用微球负载胰岛素模型肽。研究了不同负载方式对胰岛素负载效率和免疫活性的影响。结果表明，在壳聚糖固化过程中，负载胰岛素可获得较高的负载效率（56.7%）和显著的活性维持（99.4%）。随后，研究了最佳胰岛素负载微球的体外释放特性。在胃肠道环境pH条件下，模拟药物传递时间（胃内2h，肠内4h）只有32%的胰岛素释放。而在血液环境pH条件下，胰岛素释放稳定且持续时间较长（14天）。此外，胰岛素微球经含胃蛋白酶的模拟胃液处理2h后，其化学稳定性得到很好的保存。结果表明，海藻酸-壳聚糖微球可有效降低糖尿病大鼠的血糖水平，并能长期（~ 60h）保持稳定。因此，海藻酸-壳聚糖微球是一种很有前景的蛋白质或肽类药物口服给药载体。
The alginate–chitosan microspheres with narrow size distribution were prepared by membrane emulsification technique in combination with ion (Ca2+) and polymer (chitosan) solidification. The preparation procedure was observed, and the physical properties (particle size distribution, surface morphology, chitosan distribution, zeta potential) of the microspheres were characterized. Subsequently, the microspheres were employed to load model peptide of insulin. The effect of loading ways on the loading efficiency and immunological activity of insulin were investigated. It was shown that the higher loading efficiency (56.7%) and remarkable activity maintenance (99.4%) were obtained when the insulin was loaded during the chitosan solidification process (Method B). Afterward, the release profile in vitro for the optimal insulin-loaded microspheres was investigated. Under the pH conditions of gastrointestinal environment, only 32% of insulin released during the simulated transit time of drug (2h in the stomach and 4h in the intestinal). While under the pH condition of blood environment, insulin release was stable and sustained for a long time (14days). Furthermore, the chemical stability of insulin released from the microspheres was well preserved after they were treated with the simulated gastric fluid containing pepsin for 2h. Finally, the blood glucose level of diabetic rats could be effectively reduced and stably kept for a long time (∼60h) after oral administration of the insulin-loaded alginate–chitosan microspheres. Therefore, the alginate–chitosan microspheres were found to be promising vectors showing a good efficiency in oral administration of protein or peptide drugs.