Structure–property relationships in ABC-type polymer carriers: exploring drug loading and release behavior via dissipative particle dynamics simulation

Abstract

The topological architecture of polymer carriers is a critical determinant of their drug loading capacity and release characteristics. This study employed dissipative particle dynamics (DPD) simulations to systematically investigate the drug distribution and pH-responsive release behavior of three ABC-type polymer carriers with identical block compositions (where A is hydrophobic, B is pH-responsive, and C is hydrophilic) but distinct topologies: miktoarm star polymer, linear triblock copolymer, and star block copolymer. The simulation results revealed the fundamental differences in the drug distribution mechanism induced by the topological architecture of polymers. The miktoarm star polymer enables a unique “core–shell dual loading” mode, where drug molecules (doxorubicin, DOX) are simultaneously encapsulated within both the hydrophobic core and the pH-responsive intermediate layer. In contrast, within the micelles of linear and block-star copolymers, drug molecules are predominantly confined to the intermediate layer. Despite both the linear and star block copolymer systems exhibiting a “shell-loading” mode for drug distribution, the star block copolymers demonstrate a faster drug release under acidic conditions, whereas the linear block copolymers exhibit gradual drug release. Through the analysis of the interfacial electrostatic environment, we observed that a balanced ion distribution facilitates drug release in the star block copolymer system, whereas a counterion barrier arising from an overcharging effect impedes release in the linear block copolymer system. This study highlights the topological design as a robust strategy for precisely modulating both the spatial distribution and release behavior of therapeutic agents within nanocarriers.