Preparation and Antidiabetic Effect of Orally Administered Nifedipine‐Loaded Solid Lipid Nanoparticles in Fructose-Induced Diabetic Rats

• 作者: Md. Ashraf Ali Mir Imam Ibne Wahed Ranjan Kumar Barman Sabarni Sarker Shigeru Itai Shuji Noguchi Yasunori Iwao
• 来源期刊: 药理与制药(英文)
• 学科: 医学
• 关键词: FORMULATION Solid LIPID Nanoparticle Calcium Channel BLOCKER NIFEDIPINE FRUCTOSE Diabetes
• 年，卷（期）: 2018,（10）
• 页码范围: 457-471
• 页数: 15页
• 分类号: R5

摘要

The use of Nifedipine (NI), a dihydropyridine calcium channel blocker, is limited due to its poor aqueous solubility. However, NI loaded solid-lipid nanoparticles (NI-SLN) are known to exhibit suitable pharmacokinetic properties and good biocompatibility. The present investigation was designed to evaluate the effects of NI-SLN on glucose homeostasis, lipid metabolism and liver function in fructose-induced diabetic rats. NI-SLN was prepared by high pressure homogenization technique followed by lyophilization with trehalose as cryoprotectant. Diabetes was induced into rats by the administration of fructose (10%) in drinking water for six weeks. After induction of diabetes, rats were divided into four groups for the oral ingestion of NI, NI-SLN and/or vehicles and their effects on blood glucose levels, oral glucose tolerance test (OGTT), lipid profile, biochemical parameters, electrolytes and histopathology were observed. Single dose administration and treatment with NI-SLN showed significant glucose lowering efficacy in fructose-induced diabetic rats. Although NI and NI-SLN did not alter the fasting blood glucose level in normal rats, diabetic rats treated with NI-SLN resulted in significant reduction in glucose level for 24 hr. In OGTT, NI-SLN exhibited significant antihyperglycemic activity in both normal and diabetic rats. So, NI-SLN has better glucose lowering efficacy than that of pure NI in diabetic rats. The survival rates in rats among the treatment groups were 100%. Treatment with NI-SLN significantly improved lipid profiles than NI alone and the effect was dose-dependent. Administration of NI-SLN significantly reduced uric acid, creatinine levels and maintained a good cationic balance. After two weeks of NI-SLN treatment, hepatocytes regained their normal architecture, and the beneficial effect could be correlated with the reduction of SGOT and total bilirubin levels. Therefore, NI-SLN was found to be useful for the enhancement of bioavailability and exhibited profound antidiabetic activity in rats. The r