Formulation and evaluation of physicochemical characteristics of rivastigmine nanogel, cellular studies and permeability of the nasal mucosa

Abstract

Introduction: In recent years, thermosensitive hydrogel systems containing nanoparticles have been highly regarded due to their unique properties as nasal delivery systems. These systems are liquid at room temperature and undergo sol–gel transition at nasal temperature.

Object: The aim of this research was to provide hydrogels containing PLGA nanoparticles loaded with rivastigmine hydrogen tartrate (RHT) and hydrogels containing RHT loaded eudragit RL 100 nanoparticles, evaluation of physicochemical properties of nanoparticles and nanogels as well as cellular toxicity and cellular uptake of nanoparticles.

Method: The RHT nanoparticles were prepared by a nanoprecipitation technique. The nanoparticles were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD) analysis. The in vitro drug release profiles, cytotoxic effect as well as cellular uptake of nanoparticles were evaluated. Also, nanogels were prepared according to the “cold method” and analyzed in terms of physicochemical properties along with drug permeability through the sheep nasal mucosa.

Results: The mean particle size of PLGA and eudragit nanoparticles was found to be between 75.14 to 173 nm and 118 to 154 nm, respectively. FTIR, DSC , and XRPD exhibited no drug to polymer interaction through the preparation of nanoformulations. In vitro release profiles of the nanoparticles showed slow release patterns compared to the pure drug (P<0.05). Also, the results of cytotoxicity test did not show significant toxicity for pure drug and nanoparticles containing drug (P<0.05). Besides, the histograms of nanoparticles exhibited a peak shift to the right, and demonstrated that nanoparticles are efficiently taken up by A549 cells in a dose- and time-dependent manner. The prepared nanogels had a loading efficiency of 95 to 100%. Also, the results of the evaluation of drug permeability from nanogels showed good penetration for the drug (P<0.05).

Conclosion: The prepared nanoparticles showed favorable physicochemical characteristics, slow release pattern, cytocompatibility and acceptable cellular uptake. The prepared nanogels also had good physicochemical properties and good penetration through the nasal mucus tissue and seem to be able to function well in the delivery of the nasal route.