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

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2014 Aug 16

PMID 25126544

Citations 33

Authors

Deepak Sharma

Dipika Maheshwari

Gilphy Philip

Ravish Rana

Shanu Bhatia

Manisha Singh

Reema Gabrani

Sanjeev K Sharma

Javed Ali

Rakesh Kumar Sharma

Shweta Dang

Affiliations

Soon will be listed here.

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 21.7 ± 1.3% with prolonged drug release of 69.5 ± 0.8% 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.

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