Study On The Novel Bisphosphonate Liposomes And Their Effects On Macrophages

Bisphosphonates are a class of widely used drugs for treating osteoporosis and for the treatment of inflammatory diseases such as rheumatoid arthritis and osteoarthritis.At present,bisphosphonates have been developed for three generations.This paper mainly uses sodium bisphosphonates of sodium clodronate,sodium pamidronate and alendronate.Besides,it is also well established that these compounds can have significant toxic effects on macrophage cell lines in vitro.Specifically,they were incorporated inside liposome and widely used in animal models for macrophage elimination.Recently,studies have shown the use of liposomes loaded with bisphosphonates could effectively remove Tumor associated macrophage cells in murine F9 teratocarcinoma and human A673 rhabdomyosarcoma tumor models,thereby inhibiting tumor growth.Most previous study used liposomes containing conventional phospholipids and cholesterol.In this study,we studied three kinds of lipids including egg lecithin,hydrogenated lecithin,palmitic acid and cholesterol with different formulations and optimized for bisphosphonates loading optimization.We showed the new liposome formulation containing palmitic acid and cholesterol had better efficacy against macrophage elimination.Finally,we used 4T1 tumor bearing mouse tumor model to evaluate the efficacy of drug loaded liposomes.Making more macrophages depleted,thereby significantly inhibiting tumor growth.