Formulation and Optimization of Polymeric Nanoparticles for Intranasal Delivery of Lorazepam Using Box-Behnken Design:In VitroandIn VivoEvaluation

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.

Nanoparticulate Hydrogel Incorporated with Mimosa pudica Extract: Formulation and Characterization

“…The pellet was washed with deionized water twice to remove unentrapped drug from the surface of nanoparticles. Nanoparticulate pellets were redispersed in water [8].…”

Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies

“…The bag was then immersed in 50 ml of the release medium in amber colored bottles (due to light sensitivity of the drug) (Shaji & Aditi, n.d.). Because of very limited solubility of the drug, the release medium consisted of ethanol/water mixture in the ratio of 1:1 (Sharma et al, 2014). The bottles were then placed in a thermostatically controlled shaking water bath operating at 100 shake per minute and a temperature of 37 ± 0.5 C (Yang et al, 2013).…”

Development of Nanoparticulate Hydrogel Loaded with Crossandra infundibuliformis Extract

“…11 During the process, the organic phase was prepared by dissolving accurately weighed PLGA and plant extract in DMSO as organic solvent. The organic phase was then added dropwise at the rate of 1ml/min into an aqueous phase containing surfactant (PVA -0.5%) dissolved in water as aqueous solvent.…”