Thermodynamic compatibility of actives encapsulated into PEG-PLA nanoparticles: In Silico predictions and experimental verification

TL;DR

This study combines molecular dynamics simulations and Flory-Huggins theory to efficiently predict the thermodynamic compatibility of active substances with PEG-PLA nanoparticles, verified by experimental encapsulation results.

Contribution

It introduces a rapid, computationally efficient method for predicting compatibility in drug delivery systems, avoiding explicit copolymer chain modeling.

Findings

MD and Flory-Huggins accurately predict compatibility.

Predictions match experimental encapsulation efficiencies.

Method reduces time for formulation optimization.

Abstract

Achieving optimal solubility of active substances in polymeric carriers is of fundamental importance for a number of industrial applications, including targeted drug delivery within the growing field of nanomedicine. However, its experimental optimization using a trial-and-error approach is cumbersome and time-consuming. Here, an approach based on molecular dynamics (MD) simulations and the Flory-Huggins theory is proposed for rapid prediction of thermodynamic compatibility between active species and copolymers comprising hydrophilic and hydrophobic segments. In contrast to similar methods, our approach offers high computational efficiency by employing MD simulations that avoid explicit consideration of the actual copolymer chains. The accuracy of the method is demonstrated for compatibility predictions between pyrene and nile red as model dyes as well as indomethacin as model drug and copolymers containing blocks of poly(ethylene glycol) and poly(lactic acid) in different ratios. The results of the simulations are directly verified by comparison with the observed encapsulation efficiency of nanoparticles prepared by nanoprecipitation.