We describe the synthesis and analysis of dual carfilzomib and doxorubicin loaded nanoparticles in their ability to deliver both drugs to multiple myeloma tumor cells at their optimal synergistic ratio. First, to identify the optimal synergistic ratio, various molar ratios of carfilzomib to doxorubicin were screened against multiple myeloma cell lines using the Chou-Talalay method. Both therapeutic agents were then incorporated into liposomes at the identified optimal synergistic ratio of 1:1 to achieve dual drug loaded nanoparticles with a narrow size distribution of ~100 nm and with high reproducibility. Our results established that the dual drug loaded nanoparticles exhibited synergy in vitro and were more efficacious in inhibiting tumor growth in vivo than a combination of free drugs, while at the same time reducing systemic toxicity. In conclusion, this study achieved the preclinical evaluation of dual drug loaded liposomes containing carfilzomib and doxorubicin for enhanced therapeutic efficacy to improve patient outcome in multiple myeloma.

Citation Format: Basar Bilgicer, Tanyel Kiziltepe, David Omstead. Dual carfilzomib and doxorubicin carrying nanoparticles for synergistic efficacy in multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2200. doi:10.1158/1538-7445.AM2017-2200