College of Pharmacy and Research, Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, South Korea.
Department of Industrial and Physical Pharmacy, Purdue University, Heine Pharmacy Bldg, 575 W Stadium Ave, West Lafayette, IN 47907, USA.
J Control Release. 2019 May 28;302:148-159. doi: 10.1016/j.jconrel.2019.04.006. Epub 2019 Apr 4.
Carfilzomib (CFZ) is the second-in-class proteasome inhibitor with much improved efficacy and safety profiles over bortezomib in multiple myeloma patients. In expanding the utility of CFZ to solid cancer therapy, the poor aqueous solubility and in vivo instability of CFZ are considered major drawbacks. We investigated whether a nanocrystal (NC) formulation can address these issues and enhance anticancer efficacy of CFZ against breast cancer. The surface of NC was coated with albumin in order to enhance the formulation stability and drug delivery to tumors via interactions with albumin-binding proteins located in and near cancer cells. The novel albumin-coated NC formulation of CFZ (CFZ-alb NC) displayed improved metabolic stability and enhanced cellular interactions, uptake and cytotoxic effects in breast cancer cells in vitro. Consistently, CFZ-alb NC showed greater anticancer efficacy in a murine 4T1 orthotopic breast cancer model than the currently used cyclodextrin-based formulation. Overall, our results demonstrate the potential of CFZ-alb NC as a viable formulation for breast cancer therapy.
卡非佐米（CFZ）是一种新型蛋白酶体抑制剂，与硼替佐米相比，在多发性骨髓瘤患者中具有更好的疗效和安全性。为了将 CFZ 应用于实体瘤治疗，需要解决其较差的水溶性和体内不稳定性。本研究旨在探讨纳米晶体（NC）制剂是否能解决这些问题，并增强 CFZ 对乳腺癌的抗癌疗效。NC 的表面用白蛋白进行了包覆，以通过与位于癌细胞内和附近的白蛋白结合蛋白相互作用，增强制剂的稳定性和向肿瘤的递药效率。新型白蛋白包覆 CFZ 的 NC 制剂（CFZ-alb NC）显示出在体外增强了代谢稳定性和与乳腺癌细胞的相互作用、摄取和细胞毒性作用。一致的是，CFZ-alb NC 在 4T1 原位乳腺癌小鼠模型中比目前使用的环糊精制剂具有更强的抗癌疗效。总之，我们的结果表明 CFZ-alb NC 有潜力成为治疗乳腺癌的一种可行制剂。
