Insulin-Loaded pH-Sensitive Hyaluronic Acid Nanoparticles Enhance Transcellular Delivery
Insulin-Loaded pH-Sensitive Hyaluronic Acid Nanoparticles Enhance Transcellular Delivery
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DOI：
10.1208/s12249-012-9807-2
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发表时间：
2012-09-01
影响因子：
3.3
通讯作者：
Feng, Min
中科院分区：
文献类型：
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作者：
Han, Lina;Zhao, Yuefang;Feng, Min
在本研究中，我们开发了用于胰岛素输送的新型负载胰岛素的透明质酸（HA）纳米颗粒。采用反相乳液冷冻干燥法制备负载胰岛素的HA纳米粒。该方法产生了平均尺寸为 182.2 nm 的均匀小 HA 纳米颗粒群，并实现了高胰岛素包封效率（约 95%）。 pH敏感的HA纳米粒子作为口服递送载体在保护胰岛素免受胃的强酸性环境的影响，并且不破坏上皮细胞的连接完整性方面表现出优势，这保证了长期胰岛素治疗的长期安全性。转运实验结果表明，负载胰岛素的HA纳米颗粒主要通过跨细胞途径转运穿过Caco-2细胞单层，其从顶端到基底外侧的表观渗透系数与胰岛素溶液相比增加了两倍以上。 P-app（B 至 A）与 P-app（A 至 B）的流出比小于 1，表明 HA 纳米颗粒介导的胰岛素跨 Caco-2 细胞单层转运经历了主动转运。通过大鼠小肠的渗透性结果证实，HA 纳米颗粒显着增强了胰岛素通过十二指肠和回肠的转运。口服装载胰岛素的HA纳米颗粒治疗糖尿病大鼠也表现出比胰岛素溶液更强的降血糖作用。因此，这些 HA 纳米颗粒可能是口服胰岛素递送的有前途的候选者。
In the present study, we developed novel insulin-loaded hyaluronic acid (HA) nanoparticles for insulin delivery. The insulin-loaded HA nanoparticles were prepared by reverse-emulsion-freeze-drying method. This method led to a homogenous population of small HA nanoparticles with average size of 182.2 nm and achieved high insulin entrapment efficiencies (approximately 95%). The pH-sensitive HA nanoparticles as an oral delivery carrier showed advantages in protecting insulin against the strongly acidic environment of the stomach, and not destroying the junction integrity of epithelial cells which promise long-term safety for chronic insulin treatment. The results of transport experiments suggested that insulin-loaded HA nanoparticles were transported across Caco-2 cell monolayers mainly via transcellular pathway and their apparent permeability coefficient from apical to basolateral had more than twofold increase compared with insulin solution. The efflux ratio of P-app (B to A) to P-app (A to B) less than 1 demonstrated that HA nanoparticle-mediated transport of insulin across Caco-2 cell monolayers underwent active transport. The results of permeability through the rat small intestine confirmed that HA nanoparticles significantly enhanced insulin transport through the duodenum and ileum. Diabetic rats treated with oral insulin-loaded HA nanoparticles also showed stronger hypoglycemic effects than insulin solution. Therefore, these HA nanoparticles could be a promising candidate for oral insulin delivery.