Dynamics of Amphiphilic Poly(ε-Caprolactone) Micelles with Doxorubicin and Transition Temperature Predictions Using All-Atom Molecular Dynamics Simulation

Despite the advent of novel therapeutics, the efficient delivery of antineoplastic drugs remains a challenge. Biodegradable polymeric micelles represent a promising frontier by offering enhanced drug solubility, tumor targeting, and controlled release profiles. However, the underlying dynamics governing the drug encapsulation and solvation within these micellar structures is still vague and poorly understood. In this study, we used amphiphilic poly(γ-benzyloxy-ε-caprolactone)-<i>b</i>-poly(γ-2-[2-(2-methoxy ethoxy)ethoxy]ethoxy-ε-caprolactone) as a model copolymer with doxorubicin as a model drug and performed all-atom molecular dynamics simulations to understand the regulating mechanism of the encapsulation process. The results are in good agreement with the experimental results. In addition, we interpreted the dynamic behavior of the polymeric micelles and vital intermolecular interactions that play a key role in drug encapsulation. Our study provides a theoretical approach to obtain insights for designing and enhancing novel anticancer drug carriers for therapeutics.