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Tween 80 containing lipid nanoemulsions for delivery of indinavir to brain

Acta Pharmaceutica Sinica B 2013年第5期3卷 345-353页

作者： Kandadi Prabhakar Syed Muzammil Afzal Goparaboina Surender Veerabrahma Kishan Nanotechnology Laboratory Department of PharmaceuticsUniversity College of Pharmaceutical SciencesKakatiya UniversityWarangal 506009India

Indinavir is a protease inhibitor used in the treatment of HIV ***,it has limited efficacy in eradicating the virus in the brain due to efflux by P-glycoprotein(P-gp)expressed at the blood–brain barrier(BBB).The objective of this work was to develop an o/w lipid nanoemulsion(LNE)of indinavir using Tween 80 as co-emulsifier to improve its brain specific *** were prepared with different compositions and were characterized for globule size,polydispersity index,zeta potential and in vitro drug *** formulations were then evaluated for drug content,entrapment efficiency and stability after which brain uptake studies were carried out using fluorescent labeled LNEs and pharmacokinetic(PK)and tissue distribution studies were conducted after intravenous administration in *** uptake of indinavir was shown to be improved for a 1%Tween 80 containing formulation(F5)compared to a formulation containing 0.3%cholesterol(F2).In PK studies,the brain level of indinavir subsequent to administration of F5 was significantly(Po0.05)higher than produced by administration of a drug solution(2.44-fold)or a control nanoemulsion(F1)(1.48-fold)or formulation F2(1.6-fold).The increased brain specific accumulation of indinavir from F5 is probably due to enhanced low density lipoprotein-mediated endocytosis and P-gp inhibition by Tween 80 at the *** results suggest Tween 80 containing LNEs could provide a simple but effective means of delivering indinavir to brain.

关键词： Tween 80 Indinavir lipid nanoemulsions Brain delivery Therapeutic availability Fluorescent DiD oil

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