Understanding of Polydopamine Encapsulation of Hydrophobic Curcumin for Pleiotropic Drug Nanoformulation

Abstract Pleiotropic drug nanoformulation promises the enhanced efficacy of nanomedicines on the market. In this study, it is demonstrated that polydopamine (PDA)‐based drug encapsulation is a potential strategy for such nanoformulation, yet its mechanism remains poorly investigated. This study elucidates the mechanism of PDA‐encapsulated Curnanoformulations (CP NPs) using hydrophobic curcumin (Cur) as a model drug via local dopamine (DA) polymerization on self‐assembled Cur NPs. The formation of PDA‐based drug nanoformulations with the core–shell structure is comprehensively investigated by controlling the key synthetic parameters, deepening the understanding of DA polymerization in the context of drugs. An intriguing morphology evolution is proposed to be the key event in the formation of CP NPs, attributing to the Cur diffusion from the core to the shell of CP NPs. Moreover, the morphological data can be used to guide the optimization of the PDA‐based nanoformulation. In addition, the verification of soluble DA polymers in CP NPs hints at the heterogeneous nature of the excipient (i.e., PDA) of CP NPs, providing a cautionary view on the long‐term safety of PDA‐formulated drugs. In sum, this study would enable the pharmaceutical development of PDA‐encapsulated Cur nanomedicines and generalize the PDA‐based nanoformulation approach for a wider range of hydrophobic drugs.