Formulation and evaluation of metformin hydrochloride-loaded niosomes as controlled release drug delivery system
Formulation and evaluation of metformin hydrochloride-loaded niosomes as controlled release drug delivery system
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DOI：
10.3109/10717544.2013.779332
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发表时间：
2013-04-01
期刊：
影响因子：
6
通讯作者：
Wageh, Sherief
中科院分区：
文献类型：
--
作者：
Hasan, Azza A.;Madkor, Hafez;Wageh, Sherief
乳酸酸中毒是一种严重的代谢并发症，可能是由于糖尿病治疗过程中盐酸二甲双胍（MH）蓄积而引起的。本研究的目的是通过口服途径提高 MH 的生物利用度。 Span 40 和胆固醇用于通过反相蒸发技术制备负载 MH 的脂质体。磷酸二十六酯（DCP）和1,2-二油酰基-3-三甲基铵-丙烷氯化盐（DOTAP）分别用于获得带负电和带正电的囊泡。平均粒径范围为 223.5 至 384.6nm，并且在没有电荷诱导剂 (+ 16.6 +/- 1.4 mV) 和 DCP (+ 26.9 +/- 1.0 mV) 的情况下，负载 MH 的类脂质体表面带负电荷，而用 DOTAP 则带正电荷 (+8.7 +/- 1.2 mV)。在所有制剂中均观察到高包封效率。发现负载 MH 的囊泡可有效维持药物的释放，特别是带正电荷的囊泡。通过测量不同研究的 Wistar 大鼠组中葡萄糖和二甲双胍的血清值来评估负载 MH 的囊泡的生物利用度。负载 MH 的类脂质体制剂的药代动力学数据显示，与游离 MH 溶液相比，降血糖作用显着延长且强度增加。血糖水平-时间曲线上方的面积 (AAC)、最大降血糖反应和最大反应时间 (T-max) 显着更高 (p
Lactic acidosis is a serious, metabolic complication that may occur due to metformin hydrochloride (MH) accumulation during the treatment of diabetes mellitus. The aim of this study is to enhance the bioavailability of MH by oral route. Span 40 and cholesterol were used for the preparation of MH-loaded niosomes by the reverse phase evaporation technique. Dicetyl phosphate (DCP) and 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) were used to obtain negatively and positively charged vesicles, respectively. The mean particle size ranged from 223.5 to 384.6nm and the MH-loaded niosomes' surface was negatively charged in the absence of charge inducing agents (+ 16.6 +/- 1.4 mV) and also with DCP (+ 26.9 +/- 1.0 mV), while it was positively charged (+8.7 +/- 1.2 mV) with DOTAP. High entrapment efficiency was observed in all the formulations. MH-loaded niosomes were found to effectively sustain the release of drug, particularly with positively charged niosomes. The bioavailability of MH-loaded niosomes was assessed by measuring the serum values of glucose and metformin in the different studied Wistar rats groups. The pharmacokinetic data of MH-loaded niosomal preparation showed a significant prolongation and increased intensity of hypoglycemic effect more than that observed for free MH solution. Area above the blood glucose levels-time curve (AAC), maximum hypoglycemic response and time of maximum response (T-max) were significantly higher (p