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用于治疗高脂血症的阿托伐他汀ω-3脂肪酸基纳米脂质制剂

Omega-3 Fatty Acid Based Nanolipid Formulation of Atorvastatin for Treating Hyperlipidemia.

作者信息

Sreedhar Revathy, Kumar Vrinda Sasi, Bhaskaran Pillai Anil Kumar, Mangalathillam Sabitha

机构信息

Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.

Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.

出版信息

Adv Pharm Bull. 2019 Jun;9(2):271-280. doi: 10.15171/apb.2019.031. Epub 2019 Jun 1.

Abstract

In the current study, attempts have been made to formulate an omega-3 fatty acid based nanostructured lipid carriers of atorvastatin (AT), for treating hyperlipidemia; and to evaluate their antihyperlipidemic activity using in vitro and in vivo studies. Omega-3 fatty acid based AT-loaded nanolipid carriers (NLC) were formulated by the melt emulsification ultrasonication technology. The prepared NLC consist of stearic acid (as solid lipid), omega-3 fatty acid (as liquid lipid), Tween 80, poloxamer 188 (surfactants) and soya-lecithin (co-surfactant). AT loaded NLCs have a particle size of 74.76 ± 4.266 nm, a zeta potential value of -36.03 ± 1.504 mV and a high drug entrapment efficiency (EE) of 86.70 % ± 0.155. The release of AT from NLCs exhibited a sustained behaviour, which made it an ideal vehicle for drug delivery. MTT assay results indicated that NLCs are compatible with L929 (mouse fibroblast) cell lines. Anti-hyperlipidemic study showed a significant reduction in LDL and TG levels in serum with the orally administered Omega-3 fatty acid based AT loaded NLCs when compared to marketed formulation. The results demonstrated that the omega-3 fatty acid based NLC has the potential to be a promising nanomedicine for the treatment of hyperlipidemia.

摘要

在当前的研究中,已尝试制备基于ω-3脂肪酸的阿托伐他汀纳米结构脂质载体用于治疗高脂血症,并通过体外和体内研究评估其抗高脂血症活性。基于ω-3脂肪酸的载阿托伐他汀纳米脂质载体(NLC)采用熔融乳化超声技术制备。所制备的NLC由硬脂酸(作为固体脂质)、ω-3脂肪酸(作为液体脂质)、吐温80、泊洛沙姆188(表面活性剂)和大豆卵磷脂(助表面活性剂)组成。载阿托伐他汀的NLC粒径为74.76±4.266nm,ζ电位值为-36.03±1.504mV,药物包封率(EE)高达86.70%±0.155。阿托伐他汀从NLC中的释放呈现出持续的特性,使其成为理想的药物递送载体。MTT法检测结果表明NLC与L929(小鼠成纤维细胞)细胞系具有相容性。抗高脂血症研究表明,与市售制剂相比,口服基于ω-3脂肪酸的载阿托伐他汀NLC可显著降低血清中低密度脂蛋白和甘油三酯水平。结果表明,基于ω-3脂肪酸的NLC有潜力成为治疗高脂血症的一种有前景的纳米药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d44/6664121/dfc4134d45db/apb-9-271-g001.jpg

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