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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.
- Source :
-
International journal of pharmaceutics [Int J Pharm] 2013 Aug 16; Vol. 452 (1-2), pp. 300-10. Date of Electronic Publication: 2013 May 14. - Publication Year :
- 2013
-
Abstract
- 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 (5mg/ml) micelles (F1-F12) were prepared, using a Pluronic(®) 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. (1)H NMR studies confirmed OZ incorporation into micelle core. At a drug:Pluronic(®) L121:Pluronic(®) 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.<br /> (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Subjects :
- Administration, Intranasal
Animals
Antipsychotic Agents administration & dosage
Antipsychotic Agents chemistry
Benzodiazepines administration & dosage
Benzodiazepines chemistry
Drug Carriers administration & dosage
Drug Carriers chemistry
Hydrophobic and Hydrophilic Interactions
Male
Micelles
Nasal Mucosa anatomy & histology
Nasal Mucosa drug effects
Olanzapine
Poloxalene chemistry
Poloxamer chemistry
Rats
Rats, Wistar
Sheep
Tissue Distribution
Antipsychotic Agents pharmacokinetics
Benzodiazepines pharmacokinetics
Brain metabolism
Drug Carriers pharmacokinetics
Nanoparticles administration & dosage
Nanoparticles chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3476
- Volume :
- 452
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- International journal of pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 23684658
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2013.04.084