Brain targeting of olanzapine via intranasal delivery of core-shell difunctional block copolymer mixed nanomicellar carriers: In vitro characterization, ex vivo estimation of nasal toxicity and in vivo biodistribution studies

被引:117
作者
Abdelbary, Ghada Ahmed [1 ]
Tadros, Mina Ibrahim [1 ]
机构
[1] Cairo Univ, Fac Pharm, Dept Pharmaceut & Ind Pharm, Cairo 11562, Egypt
关键词
Olanzapine; Polymeric mixed micelles; Radiolabeling; Nose-to-brain delivery; In vivo biodistribution; DRUG-DELIVERY; POLYMERIC MICELLES; RELEVANCE; VESICLES; SYSTEM;
D O I
10.1016/j.ijpharm.2013.04.084
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Olanzapine (OZ) is atypical antipsychotic drug that suffers from low brain permeability due to efflux by P-glycoproteins and hepatic first-pass metabolism. The current work aimed to develop OZ-loaded micellar nanocarriers and investigate their nose-to-brain targeting potential. OZ-loaded (5 mg/ml) micelles (F1-F12) were prepared, using a Pluronic (R) mixture of L121 and P123, adopting thin-film hydration method. The micelles were evaluated for turbidity, particle size, morphology, drug-entrapment efficiency (EE%), drug-loading characteristics, in vitro drug release and ex vivo nasal toxicity in sheep. The in vivo biodistribution and pharmacokinetic studies in the brain/blood following intravenous (i.v.) and intranasal (i.n.) administrations of technetium-labeled OZ-loaded micelles and OZ-solution were evaluated in rats. Spherical micelles ranging in size from 18.97 to 380.70 nm were successfully developed. H-1 NMR studies confirmed OZ incorporation into micelle core. At a drug: Pluronic (R) L121: Pluronic (R) P123 ratio of 1: 8: 32 (F11), the micelles achieved a conciliation between kinetic and thermodynamic stability, high drug-EE%, controlled drug-release characteristics and evoked minor histopathological changes in sheep nasal mucosa. The significantly (P < 0.05) higher values for F11 micelles (i.n.); brain/blood ratio (0.92), drug targeting index (5.20), drug targeting efficiency (520.26%) and direct transport percentage (80.76%) confirm the development of a promising non-invasive OZ-loaded nose-to-brain delivery system. (C) 2013 Elsevier B. V. All rights reserved.
引用
收藏
页码:300 / 310
页数:11
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