用于胰岛素口服递送的新型聚乳酸-羟基乙酸共聚物纳米颗粒。
Novel PLGA-based nanoparticles for the oral delivery of insulin.
作者信息
Malathi Sampath, Nandhakumar Perumal, Pandiyan Velayudham, Webster Thomas J, Balasubramanian Sengottuvelan
机构信息
Department of Inorganic Chemistry, Guindy Campus, University of Madras, Chennai, Tamil Nadu, India.
Department of Veterinary Biochemistry, Madras Veterinary College, Chennai, Tamil Nadu, India.
出版信息
Int J Nanomedicine. 2015 Mar 19;10:2207-18. doi: 10.2147/IJN.S67947. eCollection 2015.
BACKGROUND
Insulin is the drug therapy for patients with insulin-dependent diabetes mellitus. A number of attempts have been made in the past to overcome the problems associated with the oral delivery of insulin, but with little success. Orally administered insulin has encountered with many difficulties such as rapid degradation and poor intestinal absorption. The potential use of D-α-tocopherol poly(ethylene glycol) 1000 succinate (TPGS)-emulsified poly(ethylene glycol) (PEG)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was investigated for sustained delivery of insulin (IS).
OBJECTIVE
To investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs) as a potential drug carrier for the oral delivery of insulin.
METHODS
A series of biodegradable low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6]) copolymers were synthesized by melt polycondensation. The commercial insulin-loaded TPGS-emulsified PEG-capped PLGA NPs (ISTPPLG NPs) were synthesized by water-oil-water emulsion solvent evaporation method. The physical and chemical properties of PLGA copolymers, particle size, zeta potential, and morphology of the NPs were examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by oral administration.
RESULTS
The maximum encapsulation efficiency of ISTPPLG6 NPs was 78.6% ± 1.2%, and the mean diameter of the NPs was 180 ± 20 nm. The serum glucose level was significantly (twofold) decreased on treatment with ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30) NPs when compared to that of free insulin-treated diabetic rats. The results show that the oral administration of ISTPPLG6 NPs is an effective method of reducing serum glucose level for a period of 24 hours. Histopathological studies reveal that ISTPPLG NPs could restore the damage caused by streptozotocin in the liver, kidneys, and pancreas, indicating its biocompatibility and regenerative effects.
CONCLUSION
ISTPPLG6 NPs can act as potential drug carriers for the oral delivery of insulin.
背景
胰岛素是胰岛素依赖型糖尿病患者的药物治疗手段。过去人们曾多次尝试克服胰岛素口服给药相关的问题，但成效甚微。口服胰岛素面临诸多困难，如快速降解和肠道吸收不佳。研究了聚乙二醇1000琥珀酸酯维生素E（TPGS）乳化的聚乙二醇（PEG）封端的聚乳酸-乙醇酸共聚物（PLGA）纳米粒（NPs）用于胰岛素（IS）持续递送的潜在用途。
目的
研究TPGS乳化的PEG封端的PLGA纳米粒（TPPLG NPs）作为胰岛素口服给药潜在药物载体的效果。
方法
通过熔融缩聚合成了一系列可生物降解的低分子量PLGA（80/20 [PLG4]和70/30 [PLG6]）共聚物。采用水-油-水乳液溶剂蒸发法合成了市售载胰岛素的TPGS乳化的PEG封端的PLGA纳米粒（ISTPPLG NPs）。研究了PLGA共聚物的理化性质、纳米粒的粒径、ζ电位和形态。通过口服给药在糖尿病大鼠中开展ISTPPLG NPs的体内研究。
结果
ISTPPLG6 NPs的最大包封率为78.6%±1.2%，纳米粒的平均直径为180±20 nm。与游离胰岛素治疗的糖尿病大鼠相比，用ISTPPLG NPs治疗后血清葡萄糖水平显著降低（两倍），载胰岛素的PLGA（70/30）纳米粒治疗后降低了三倍。结果表明，口服ISTPPLG6 NPs是在24小时内降低血清葡萄糖水平的有效方法。组织病理学研究表明，ISTPPLG NPs可修复链脲佐菌素对肝脏、肾脏和胰腺造成的损伤，表明其生物相容性和再生作用。
结论
ISTPPLG6 NPs可作为胰岛素口服给药的潜在药物载体。
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