Can drug molecules diffuse into the core of micelles?

The entrapment efficiency of a drug into self-assembled polymeric micelles is commonly found to be extremely low. Drug diffusion into the core of micelles is an important process that affects the micelle loading capacity and efficiency of hydrophobic drugs. Herein, dissipative particle dynamics (DPD) simulations are carried out to study drug diffusion abilities into the core of micelles after the core-shell structure of the micelle is formed, which is the key issue that affects drug loading efficiency. Topological structures of the drug, the hydrophobic block length of the polymer, as well as the compatibility between the drug and the hydrophobic block have significant effects on drug loading efficiencies and drug distributions inside micelles. In particular, the interaction parameter of 10 between the drug and hydrophobic block A results in 100% drug loading efficiency and a very homogeneous distribution of drug molecules in the core of the micelles. We also provide an insight into the relationship between drug loading efficiency and micelle stability, which can facilitate the development of stable drug loaded micelles. The present study provides a mechanistic study of micellar drug loading on the microscale level, which may provide ideas for future experimental preparation of stable drug loaded micelles with high drug loading efficiencies.