Enhancing the Encapsulation Performances of Liposomes for Amphiphilic Copolymers by Computer Simulations

Liposomes, which encapsulate drugs into an inner aqueous core and demonstrate high drug-loading capacity, have attracted considerable interest in the field of drug delivery. Herein, the encapsulation processes for amphiphilic copolymers within liposomes have been investigated systematically to enhance the encapsulation capacity and optimize the structures using dissipative particle dynamics simulations. The results indicate that the physicochemical properties of lipids, receptors, and amphiphilic copolymers collectively determine the encapsulation behaviors of liposomes. Adjusting the hydrophobic interaction between hydrophobic tails of lipids (receptors) and hydrophobic blocks of copolymers, along with modulating the specific interaction between ligands and the functional head groups of receptors, can lead to various encapsulation capacities. Significantly, a medium hydrophobic interaction strength or a strong specific interaction is conducive to achieving a higher degree of encapsulation for amphiphilic copolymers. Furthermore, varying the key parameters, such as the hydrophobic interaction, the specific interaction, as well as the concentrations of lipids and receptors, can induce seven typical aggregate structures: heterogeneous, fully encapsulated, partially encapsulated, saturated-encapsulated, unsaturated-encapsulated, multilamellar, and column-like structures. The final phase diagrams are also constructed to provide a guideline for designing various structures of liposomes encapsulated with amphiphilic copolymers. These results significantly contribute to the illumination of strategies for the rational construction of the self-assembly system that facilitates the efficient encapsulation of amphiphilic copolymers within the inner aqueous core of liposomes, thereby providing valuable insights into the optimal design of liposome carriers for future biomedical applications.