Enhancement of oral insulin bioavailability: in vitro and in vivo assessment of nanoporous stimuli-responsive hydrogel microparticles
Enhancement of oral insulin bioavailability: in vitro and in vivo assessment of nanoporous stimuli-responsive hydrogel microparticles
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DOI：
10.1517/17425247.2016.1160889
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发表时间：
2016-05-01
影响因子：
6.6
通讯作者：
Buang, Fhataheya
中科院分区：
文献类型：
--
作者：
Ahmad, Naveed;Amin, Mohd Cairul Iqbal Mohd;Buang, Fhataheya
目的：口服胰岛素会导致胃肠道降解和肠上皮吸收不足，导致生物利用度差。这项研究需要体外和体内评估刺激反应性水凝胶微粒（MPs），试图绕过胃肠道屏障，提高口服胰岛素的生物利用度。方法：对细菌纤维素-g-聚丙烯酸（BC-g-P(AA)）水凝胶MPs的形态、溶胀、包封效率（EE）、体外胰岛素释放和酶抑制进行评价。研究了胰岛素在离体小肠组织中的黏附、胰岛素的降解和转运。研究了MPs在Caco-2/HT29-MTX单层膜中对细胞旁转运的影响。研究了胰岛素负载MPs在糖尿病大鼠体内的降糖作用和药代动力学。结果：水凝胶MPs有效包裹胰岛素（EE高达84%），并表现出ph响应的体外释放。MPs降低了胰蛋白酶的蛋白水解活性（高达60%）。胰岛素跨单层转运增加了5.9倍。胃肠道组织的组织学评估证实了MPs的无毒性。与胰岛素溶液相比，口服胰岛素负载MPs具有更高的降糖效果，并且胰岛素的相对口服生物利用度提高了7.45倍。结论：BC-g-P(AA) MPs是克服口服胰岛素递送障碍和提高其生物利用度的有前景的生物材料。
Objective: Oral insulin administration suffers gastrointestinal tract (GIT) degradation and inadequate absorption from the intestinal epithelium resulting in poor bioavailability. This study entails in vitro and in vivo assessment of stimuli-responsive hydrogel microparticles (MPs) in an attempt to circumvent GI barrier and enhance oral insulin bioavailability.Methods: Bacterial cellulose-g-poly(acrylic acid) (BC-g-P(AA)) hydrogel MPs were evaluated for morphology, swelling, entrapment efficiency (EE), in vitro insulin release and enzyme inhibition. The ex vivo mucoadhesion, insulin degradation and transport were investigated in excised intestinal tissues. The effect of MPs on paracellular transport was studied in Caco-2/HT29-MTX monolayers. The in vivo hypoglycemic effect and pharmacokinetics of insulin-loaded MPs were investigated in diabetic rats.Results: Hydrogel MPs efficiently entrapped insulin (EE up to 84%) and exhibited pH-responsive in vitro release. The MPs decreased the proteolytic activity of trypsin (up to 60%). Insulin transport across monolayers was increased up to 5.9-times by MPs. Histological assessment of GI tissues confirmed the non-toxicity of MPs. Orally administered insulin-loaded MPs showed higher hypoglycemic effect as compared to insulin solution and enhanced relative oral bioavailability of insulin up to 7.45-times.Conclusion: These findings suggest that BC-g-P(AA) MPs are promising biomaterials to overcome the barriers of oral insulin delivery and enhancing its bioavailability.