Encapsulation and Delivery of Dimethylcurcumin by Using Nanoparticles of a Polyethylene‐Glycol‐Based Dimethylcurcumin Prodrug
Chao Lai, Hang Hu, Defeng Xu
Abstract
Abstract Dimethylcurcumin (DMC) is a synthetic curcuminoid which can enhance androgen receptor (AR) degradation to suppress AR‐associated cancers. However, the extremely poor water solubility and low biocompatibility of DMC significantly limit its biomedical applications. Herein, a water soluble DMC prodrug mPEG‐DMC (7.4 %) with DMC loading content of 7.4 % was synthesized and further used for preparation of free DMC loaded nanoparticles (NPs) for delivery of both covalently bound and free DMC. mPEG‐DMC (7.4 %) can self‐assemble into nanoparticles in aqueous solution and can encapsulate free DMC with high drug loading content and encapsulation efficiency. The average hydrodynamic diameters of the prepared NPs are between 90 and 140 nm, and increase with increasing DMC loading content. The in vitro drug release study shows that the DMC@mPEG‐DMC (15.5 %) and DMC@mPEG‐DMC (18.6 %) NPs exhibit pH‐triggered DMC release behaviors. The cellular uptake study shows that DMC@mPEG‐DMC (18.6 %) NPs exhibit enhanced cellular uptake as compared to free DMC and DMC@mPEG‐DMC (15.5 %) NPs. DMC@mPEG‐DMC (15.5 %) and DMC@mPEG‐DMC (18.6 %) NPs exhibit similar cytotoxicity and AR protein suppression effect on HepG2 cells and 22Rv1 cells as compared to free DMC. The DMC@mPEG‐DMC (15.5 %) and DMC@mPEG‐DMC (18.6 %) NPs developed in this work provide two water soluble and effective nanoformulations of DMC.