Abstract
Multiple myeloma (MM), a plasma cell cancer in bone marrow, remains an incurable disease. Melphalan, an alkylating agent, is a conventional anticancer drug that is still widely used for MM treatment in clinics. However, melphalan-induced organ toxicity and side effects are common. In this study, we loaded melphalan into a liposomal capsule and constituted liposomal melphalan (liposomal MEL). Liposomal MEL particles were approximately 120 nm in size and stable in vitro. The liposomal particles could be effectively taken up by MM cells. In vitro cytotoxicity assays using MM cell lines and primary MM cells showed that liposomal MEL exhibited similar anti-MM activity compared to an equivalent amount of free melphalan (free MEL) compound. In animal models, liposomal particles had bone marrow enrichment and prolonged half-life in vivo. Liposomal MEL exposure resulted in less liver and colon organ toxicity than exposure to an equivalent amount of free MEL-treated mice. Importantly, liposomal MEL had potent anti-MM activity in vivo in a human MM xenograft mouse model. Overall, our findings suggested that liposome-encapsulated melphalan was an effective drug modification of the melphalan compound and showed promise in MM treatment.