Pharmaceutics Research Center, Kerman University of Medical Sciences, Kerman.
Daru. 2011;19(6):404-11.
Encapsulation of human insulin in lipid vesicular systems such as niosomes was sought as a route to protect this protein against proteolytic enzymes and to improve its oral bioavailability. The purpose of this study was to assess the effect of insulin encapsulation in niosomes on oral bioavailability in diabetic rats.
Recombinant human insulin was entrapped in multilamellar niosomes composed of polyoxyethylene alkyl ether surfactants (Brij 52 and Brij 92) or sorbitan monostearate (Span 60) and cholesterol. The amount of insulin released in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF) were measured at 37°C. The protection of entrapped insulin against pepsin, α-chymotrypsin and trypsin were evaluated in comparison with free insulin solution. Diabetes was induced by IP injection of streptozotocin (65 mg/kg) in male wistar rats and effects of orally administered niosomes and subcutaneously injected insulin on hypoglycemia and elevation of insulin levels in serum were compared.
The extent and rate of insulin release from Brij 92 and Span 60 vesicles were lower than that of Brij 52 niosomes (P<0.05). Vesicles protected insulin in comparison with free insulin solution against proteolytic enzymes (P<0.05) significantly. Animals treated with oral niosome-encapsulated insulin (100 IU/kg) showed decreased levels of blood glucose and elevated serum insulin, which in the case of Brij 92 niosomes, hypoglycemic effect was significant (P<0.05). Niosomes were also stable in solubilizing bile salt solutions and could effectively prolong the release of insulin in both SGF and SIF. Results of this study showed that niosomes may be utilized as oral carriers of insulin; however, to increase bioavailability of insulin, further studies on the protease inhibitor co-encapsulation in niosomal formulations might be helpful.
将人胰岛素包裹在脂质囊泡系统（如非离子型脂质体）中，旨在保护这种蛋白质免受蛋白酶的破坏，并提高其口服生物利用度。本研究旨在评估胰岛素在非离子型脂质体中的包封对糖尿病大鼠口服生物利用度的影响。
重组人胰岛素被包封在由聚氧乙烯烷基醚表面活性剂（Brij 52 和 Brij 92）或山梨醇单硬脂酸酯（Span 60）和胆固醇组成的多层非离子型脂质体中。在 37°C 下测量在模拟肠液（SIF）和模拟胃液（SGF）中释放的胰岛素量。与游离胰岛素溶液相比，评估了包封胰岛素对胃蛋白酶、α-糜蛋白酶和胰蛋白酶的保护作用。雄性 Wistar 大鼠通过腹腔注射链脲佐菌素（65mg/kg）诱导糖尿病，并比较了口服非离子型脂质体和皮下注射胰岛素对低血糖和血清胰岛素水平升高的影响。
Brij 92 和 Span 60 囊泡中胰岛素的释放程度和释放速度低于 Brij 52 非离子型脂质体（P<0.05）。与游离胰岛素溶液相比，囊泡显著保护胰岛素免受蛋白酶的破坏（P<0.05）。用口服非离子型脂质体包封胰岛素（100IU/kg）治疗的动物血糖水平降低，血清胰岛素水平升高，其中 Brij 92 非离子型脂质体的降血糖作用显著（P<0.05）。非离子型脂质体在溶解胆汁盐溶液中也很稳定，可以有效地延长胰岛素在 SGF 和 SIF 中的释放。本研究结果表明，非离子型脂质体可用作胰岛素的口服载体；然而，为了提高胰岛素的生物利用度，进一步研究蛋白酶抑制剂在非离子型脂质体制剂中的共同包封可能会有所帮助。
