Novel Curcumin Derivative-Decorated Ultralong-Circulating Paclitaxel Nanoparticles: A Novel Delivery System with Superior Anticancer Efficacy and Safety
Yumeng Wei, Mingtang Zeng, Chao Pi, Hongping Shen, Jiyuan Yuan, Ying Zuo, Jie Wen, Pu Guo, Wenmei Zhao, Ke Li, Zhilian Su, Xinjie Song, Shaozhi Fu, Robert J Lee, Ling Zhao
Abstract
Purpose: Paclitaxel (PTX) has been widely utilized for the treatment of breast cancer. However, drawbacks, such as poor aqueous solubility, rapid blood clearance and severe toxicity, greatly reduce its efficacy and safety. Herein, a novel self-developed curcumin derivative (CUD) was chosen as the carrier to develop a long-acting PTX nano-delivery system ( [email protected] ) in order to improve its pharmacokinetic behavior, anti-breast cancer efficacy and safety. Methods: [email protected] was prepared using solid dispersion and ultrasonic technology. Relevant physical and chemical properties, including stability and release behavior, were characterized. The clearance of [email protected] in vivo was studied by pharmacokinetic experiments. The anti-tumor activity of [email protected] was investigated in vitro and in vivo. Hemolysis experiments, acute toxicity and cumulative toxicity studies were performed in mice to determine the safety of [email protected] Results: The average particle size, PDI, Zeta potential, encapsulation efficiency and loading efficiency of the [email protected] were 238.5 ± 4.79 nm, 0.225 ± 0.011, − 33.8 ± 1.26 mV, 94.20 ± 0.49% and 10.98 ± 0.31%, respectively. [email protected] was found to be stable at room temperature for half a year. The cumulative release rates of [email protected] at 24, 96 and 168 h were 17.98 ± 2.60, 57.09 ± 2.32 and 72.66 ± 4.16%, respectively, which were adherent to zero-order kinetics. T 1/2 , MRT (0-t) and AUC (0-t) of the [email protected] group were 4.03-fold (44.293 h), 7.78-fold (38.444 h) and 6.18-fold (14.716 mg/L*h) of the PTX group, respectively. [email protected] group demonstrated stronger anti-breast cancer activity than the PTX group. Importantly, the [email protected] group was safer compared to the PTX group both in vitro and in vivo. Conclusion: [email protected] was verified as promising therapeutic nanoparticles for breast cancer and provided a novel strategy to solve the problem of low efficacy and poor safety of clinical chemotherapy drugs. Graphical Abstract: Keywords: breast cancer, long-acting, paclitaxel nanoparticles, curcumin derivative