Homoharringtonine delivered by high proportion PEG of long- circulating liposomes inhibits RPMI8226 multiple myeloma cells in vitro and in vivo

摘要

Multiple myeloma (MM) remains an incurable disease in most patients. Homoharringtonine (HHT) is a natural alkaloid produced by various Cephalotaxus species, and is approved by the United States of America Food and Drug Administration to treat patients with acute and chronic myeloid lymphoma. The aim of this study was to develop the high proportion polyethyleneglycol (PEG) of long-circulating HHT liposomes (LCL-HHT-H-PEG) and investigate its therapeutic applicability in vitro and in vivo against RPMI8226 MM. The optimized formulation of LCL-HHT-H-PEG showed a higher association with cytotoxicity against MM RPMI8226 cells than those of low proportion PEG of long-circulating HHT liposomes, liposome-encapsulated-HHT, micelle-HHT, and HHT in vitro. Therapeutic experiments in severe combined immunodeficient mice implanted with MM RPMI8226 cells by the subcutaeous route showed the significant inhibition of tumor growth in LCL-HHT-H-PEG group compared with the HHT group, and other control groups. The analysis of flow cytometry and transmission electron microscopy indicated that LCL-HHT-H-PEG exerted the cytotoxicity against MM by inducing the MM apoptosis in vitro and in vivo. This study suggests that our developed LCL-HHT-H-PEG may be regarded as a promising nano-device to deliver anti-MM drug HHT for treatment of MM patients.