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BioMed Research International
Volume 2014, Article ID 156010, 14 pages
http://dx.doi.org/10.1155/2014/156010
Research Article

Formulation and Optimization of Polymeric Nanoparticles for Intranasal Delivery of Lorazepam Using Box-Behnken Design: In Vitro and In Vivo Evaluation

1Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sector 62, Noida, Uttar Pradesh 201307, India
2Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India
3Division of CBRN Defense, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Marg, Delhi 110054, India

Received 28 February 2014; Revised 28 May 2014; Accepted 2 June 2014; Published 14 July 2014

Academic Editor: Weiguo Dai

Copyright © 2014 Deepak Sharma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The aim of the present study was to optimize lorazepam loaded PLGA nanoparticles (Lzp-PLGA-NPs) by investigating the effect of process variables on the response using Box-Behnken design. Effect of four independent factors, that is, polymer, surfactant, drug, and aqueous/organic ratio, was studied on two dependent responses, that is, z-average and % drug entrapment. Lzp-PLGA-NPs were successfully developed by nanoprecipitation method using PLGA as polymer, poloxamer as surfactant and acetone as organic phase. NPs were characterized for particle size, zeta potential, % drug entrapment, drug release behavior, TEM, and cell viability. Lzp-PLGA-NPs were characterized for drug polymer interaction using FTIR. The developed NPs showed nearly spherical shape with z-average 167–318 d·nm, PDI below 0.441, and −18.4 mV zeta potential with maximum % drug entrapment of 90.1%. In vitro drug release behavior followed Korsmeyer-Peppas model and showed initial burst release of with prolonged drug release of from optimized NPs up to 24 h. In vitro drug release data was found in agreement with ex vivo permeation data through sheep nasal mucosa. In vitro cell viability study on Vero cell line confirmed the safety of optimized NPs. Optimized Lzp-PLGA-NPs were radiolabelled with Technitium-99m for scintigraphy imaging and biodistribution studies in Sprague-Dawley rats to establish nose-to-brain pathway.