Lactoferrin-modified PLGA nanoparticles for pregabalin: development, characterization, in vitro targeting and pharmacodynamic evaluation.

Abstract

Over the years the intranasal drug delivery route has emerged as an effective strategy for drug delivery in the brain. The present study reports the development of Pregabalin-loaded nanoparticles of Poly lactic-co-glycolic acid, surface modified with lactoferrin for targeting brain cells. Lactoferrin was conjugated using Cyanamide 1-Ethyl-3-3-dimethyl aminopropyl carbodiimide and N-hydroxy Succinimide. The physicochemical properties of the nanoparticles were examined and the results showed a particle size of 152.1 ± 1.3 nm, Polydispersity Index 0.146, and surface charge of -17.9 ± 0.98 mV. In vitro, release data in Phosphate Buffer Saline (pH 7.4) and Simulated Nasal Fluid (pH 5.5) suggested that the nanoparticles showed sustained release of the drug (86.92 ± 1.4%) for 48 h. In vitro, cytotoxicity on (RPMI 2650 and Neuro-2a cells) and histopathological evaluation on goat nasal mucosa showed that the formulation was nontoxic. Results from flow cytometry and confocal microscopy confirmed that the cells readily took up modified nanoparticles compared to plain PLGA nanoparticles. The neuroprotective effect of Lf-PLGA nanoparticles was evaluated in Neuro-2a cells concerning Nitric oxide generation in response to lipopolysaccharide. Pharmacodynamic analysis on mice showed enhanced targeting of the drug and the average time of different phases of convulsion was also reduced.