The Role of Nanoparticle in Brain Permeability: An in-vitro BBB Model

Abstract

Membrane permeability and P-glycoprotein (P-gp) efflux system are regulating factors in the drug brain penetration. Recently, some drug delivery systems have been developed to overcome these limitations. In this study, Metoclopramid has been encapsulated in PLGA nanoparticles using the emulsification/solvent evaporation technique for in vitro evaluation of the effect of PLGA nanoparticles on BBB permeability. Subsequently, prepared nanoparticles were characterized using PCS, TEM, FT-IR, DSC and XRD techniques and in vitro cell permeability of optimum formulation was evaluated using MDCK cell line as BBB model. Data investigation showed that prepared nanoparticles have the entrapment efficiency of 50%. PCS investigation showed that prepared nanoparticles have an average size of approximately 150±14 nm and a relatively monodisperse distribution. TEM micrographs of the samples showed spherical shape and smooth surface with a particle size of nanometric range. Through DSC thermograms and XRD diffractograms analysis, it was demonstrated that there was no crystalline form of the drug in the loaded formulation. In vitro cytotoxicity of the formulations on MDCK cell line demonstrated the greater crossing of metoclopramide in the form of nanoparticle in comparison with the free metoclopramide. Further investigation demonstrated that the PLGA nanoparticles may act as a Pgp substrate