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Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: In vitro and in vivo studies

Paper ID Volume ID Publish Year Pages File Format Full-Text
673 57 2011 8 PDF Available
Title
Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: In vitro and in vivo studies
Abstract

Olanzapine (OZ) is a second-generation or atypical antipsychotic which selectively binds to central dopamine D2 and serotonin (5-HT2c) receptors. It has poor bioavailability due to hepatic first-pass metabolism and low permeability into the brain due to efflux by P-glycoproteins. The present investigation aimed to prepare a nanoparticulate drug delivery system of OZ using poly(lactic-co-glycolic acid) (PLGA) for direct nose-to-brain delivery to provide brain targeting and sustained release. PLGA nanoparticles (NP) were prepared by the nanoprecipitation technique and characterized by entrapment efficiency, particle size, zeta potential, modulated temperature differential scanning calorimetry (MTDSC) and X-ray diffraction (XRD) studies. The NP were evaluated for in vitro release, ex vivo diffusion, toxicity and pharmacokinetic studies. The NP were 91.2 ± 5.2 nm in diameter and had entrapment efficiency 68.91 ± 2.31%. MTDSC studies indicated broadening of the drug peak and a shift in the polymer peak, possibly due to physical interaction or H-bonding between the carbonyl groups of PLGA and the NH groups of OZ, and also due to the plasticization effect of OZ on PLGA. XRD studies indicated a decrease in the crystallinity of OZ or amorphization. In vitro drug release showed a biphasic pattern with initial burst release and, later, sustained release (43.26 ± 0.156% after 120 h), following the Fickian diffusion-based release mechanism. Ex vivo diffusion through sheep nasal mucosa showed 13.21 ± 1.59% of drug diffusion in 210 min from NP. Histopathological study of sheep nasal mucosa showed no significant adverse effect of OZ-loaded NP. In vivo pharmacokinetic studies showed 6.35 and 10.86 times higher uptake of intranasally delivered NP than OZ solution delivered through intravenous (IV) and intranasal (IN) route, respectively. These results proved that OZ could be transported directly to the brain after IN delivery of PLGA NP, enhanced drug concentration in the brain and would therefore be effective in improving the treatment of central nervous system disorders.

Graphical abstractThe images illustrate the histopathological condition of nasal mucosa after 2 h exposure of (A, negative control) PBS pH 6.4 (B, positive control) IPA (C) drug solution and (D) drug-loaded NP. The arrows in (B) indicate the change in histopathology of the mucosa. Some cilias were detached when treated with drug solution (C). No change in the mucosal histopathology was observed when treated with drug-loaded NP (D).Figure optionsDownload full-size imageDownload high-quality image (252 K)Download as PowerPoint slide

Keywords
Olanzapine; PLGA; Nanoparticles; Nose-to-brain delivery; Nasal toxicity
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Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: In vitro and in vivo studies
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 7, Issue 12, December 2011, Pages 4169–4176
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us