Dissipative particle dynamics study on amphiphilic block copolymers induced multi-geometry aggregates of the hydrophobic drugs

The micelles of hydrophobic drugs and amphiphilic copolymers, characterized by high drug loading capacity and multi-geometry morphologies, have garnered significant interest in biomedical applications. Herein, we systematically investigated the cooperative assembly processes of hydrophobic drugs and amphiphilic copolymers using dissipative particle dynamics simulations to optimize micelle formation. The results indicated that the physicochemical properties, including drug concentrations, prodrug strategies, the sequence length of amphiphilic copolymers, and the compatibility between drugs and copolymers, significantly influenced the characteristics of micelles. Optimizing the sequence length of amphiphilic copolymers can enhance the loading capacity of hydrophobic drugs, with shorter sequence length favoring the loading of hydrophobic drugs and medium sequence length facilitating the loading of hydrophilic prodrug-modified hydrophobic drugs. Furthermore, when loading hydrophobic drugs, the micelles preferably exhibit the spherical morphologies, and the specific distribution pattern of the loaded drugs can be attained by adjusting the sequence length and the interaction strength between drugs and hydrophobic components of copolymers. When loading hydrophilic prodrug-modified drugs, a variety of morphologies including mixtures, vesosomes, vesicles, multi-core structures, spherical and ring-like structures, can be achieved by adjusting parameters such as sequence length, prodrug structure, and the interaction strength between the prodrugs and hydrophilic components of copolymers. These findings offer an effective approach for constructing controllable carriers of hydrophobic drugs, providing valuable insights for the design and development of hydrophobic drug delivery systems in experimental research and biomedical applications.