Enhanced Efficacy and Safety: Cabazitaxel Nanodispersions as a Novel Therapeutic Platform against Prostate Cancer

Cabazitaxel (CTX) is primarily used in the clinical treatment of prostate cancer. The clinical CTX injection (Jevtana®) contains the solubilizer Tween 80, which can lead to serious toxic side effects during intravenous injection. This study developed a novel nanodelivery system for encapsulating CTX, eliminating the need for Tween 80 and addressing current clinical challenges associated with CTX use. The nanodelivery system uses the hydrophilic polymer polyvinylpyrrolidone K12 (PVP K12) as a dispersing agent and a small amount of highly biocompatible sodium cholesteryl sulfate (SCS) as a stabilizer, forming a cabazitaxel nanodispersion (CTX-NP) through the water dispersion method. The CTX-NP exhibited a spherical shape, uniform distribution, a particle size of 128.90 ± 0.42 nm, a PDI of 0.14 ± 0.01, a zeta potential of -65.88 ± 1.23 mV, and a drug encapsulation efficiency of 97.58 ± 0.58%. Furthermore, hemolysis, vascular irritation, and maximum tolerated dose (MTD) experiments indicated that CTX-NP has good biocompatibility compared to cabazitaxel-Tween injection (CTX-TW). The pharmacokinetic studies in rats revealed that, compared to CTX-TW, CTX-NP had an extended half-life (T_1/2), mean residence time (MRT), and a larger area under the drug concentration-time curve (AUC). In the RM-1 prostate cancer mouse model, compared with CTX-TW, the high-dose CTX-NP group showed better tumor inhibition with an inhibition rate of 79.48%, indicating that CTX-NP could achieve superior anti-tumor effects by increasing the administered dose.