Olaparib is a selective poly (ADP-ribose) polymerase inhibitor. However, its clinical application is hindered by low solubility and undesired pharmacokinetic profiles (e.g.
, relatively short circulation). Therefore, the present study aims to exploit polymeric micelles as a safe solubilizer and nanocarrier of olaparib, in order to improve its solubility and pharmacokinetics. Poly (ε-caprolactone)- co -poly (benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate), i.
e., benzyl-functionalized trimethylene carbonate)- b -poly (ethylene glycol) (P(CL- co -TMC-Bz)-PEG), was synthesized by ring-opening polymerization, and used to prepare the π-π-stacked polymeric micelles for olaparib encapsulation. A series of olaparib-loaded micelles with different polymer concentrations and wt% loadings were prepared using different methods to investigate the effect of formulation variables on the size of polymeric micelles and drug loadings.
In addition, the in vitro release of olaparib from the micelles, and the cytotoxicity of micellar olaparib formulations on the SKOV3 tumor cell line were evaluated by UV spectrophotometry and CCK-8 assay, respectively. Finally, the blood circulation kinetics and side effects of the incorporated olaparib in the micelles and free olaparib were investigated in SD rats using ultra-high performance liquid chromatography analysis and H&E staining, respectively. It was found that P(CL11- co -TMC-Bz5)-PEG micelles served as a safe and excellent solubilizer for olaparib,.
