Bisphosphonate-functionalized micelles for targeted delivery of curcumin to metastatic bone cancer

Metastatic (secondary) bone cancer is one of the major causes of death in patients with advanced cancer. A lack of options for the targeted delivery of a desired therapeutic payload to multiple tumour modules located in the bone is still one of the foremost hurdles in the treatment/prevention of metastatic bone cancer. Curcumin has a proven anticancer potential with known challenges for application as a pharmaceutical agent. We have previously shown that micellar formulations could overcome some of these challenges and enhances its anti-cancer activity. In this study, we have developed a targeted drug delivery system using bisphosphonate (alendronate) conjugated Pluronic F127 micelles that could efficiently target, and specifically deliver curcumin to the osteolytic tumour microenvironment in the bone. Characterization of the formulation of curcumin-encapsulated alendronate-conjugated micelles demonstrated that the micelles have nanoscale size (similar to 27 nm) with a positive surface charge (+2.87 mV) and 4% drug loading. The alendronate-conjugated micelles showed significant bone-targeting potential. Rapid binding of the micelles to hydroxyapatite surface suggested that these nanoparticles are promising carriers for effective and targeted delivery of curcumin to osteolytic tumours in the bone.