Investigation of pH-dependent Paclitaxel delivery mechanism employing Chitosan-Eudragit bioresponsive nanocarriers: a molecular dynamics simulation

Abstract

Before embarking on any experimental research endeavor, it is advisable to do a mathematical computation and thoroughly examine the methodology. Despite the use of polymeric nanocarriers, the regulation of bioavailability and drug release at the disease site remains insufficient. Several effective methods have been devised to address this issue, including the creation of polymeric nanocarriers that can react to stimuli such as redox potential, temperature, pH, and light. The present study has been utilized all-atom molecular dynamics (AA-MD) and coarse-grained molecular dynamics (CG-MD) methods and illustrated the drug release mechanism, which is influenced by pH, for Chitosan-Eudragit bioresponsive nanocarriers. The aim of current work is to study the molecular mechanism and atomistic interactions of PAX delivery using a Chitosan-Eudragit carrier. The ability of Eudragit polymers to dissolve in various organic solvents employed in the process of solvent evaporation is a crucial benefit in enhancing the solubility of pharmaceuticals. This study investigated the use of Chitosan-Eudragit nanocarriers for delivering an anti-tumor drug, namely Paclitaxel (PAX). Upon analyzing several significant factors affecting the stability of the drug and nanocarrier, it has been shown that the level of stability is more significant in the neutral state than the acidic state. Furthermore, the system exhibits higher stability in the neutral state. The used Chitosan-Eudragit nanocarriers exhibit a stable structure under alkaline conditions, but undergo deformation and release their payloads under acidic conditions. It was demonstrated that the in silico analysis of anti-tumor drugs and carriers’ integration could be quantified and validated by experimental results (from previous works) at an acceptable level.