Anticancer Effect of Curcumin Liposomes Against Osteosarcoma and Synergistic Effect of Curcumin with Ceramide 6

Osteosarcoma (OS) accounts for approximately 20% of all bone cancers and it develops during the period of rapid growth in adolescence. Curcumin is being used as an anticancer drug against broad spectrum of tumors but its nanoformulation potential is not fully explored to treat OS. The drug is water insoluble that limits the bioavailability. In present work, an effective delivery route is through encapsulation in cyclodextrins followed by a second encapsulation in liposomes. Anticancer potential of curcumin liposomes in monolayer culture system (two dimensional) and spheroid culture system (three dimensional) has been explored. DMSO-curcumin (free drug) induced autophagic cell death in OS whereas liposomal curcumin initiates the caspase cascade that leads to apoptotic cell death in vitro as well as in vivo. Curcumin has already been shown to act by inducing ceramide generation in many cancer cell lines. Ceramide 6 (C6) is a sphingolipid with anticancer potential. We encapsulated curcumin and C6 in liposomes to estimate combinatorial effect against osteosarcoma cell lines. Curcumin and ceramide 6 show synergistic anticancer effect when encapsulated together. Major limitation in cancer drug delivery is inability of the delivery vehicle to reach center of the solid tumor due to lack of blood circulation and lymphatic system. To mimic the three dimensional tumor model, osteosarcoma spheroid culture system was optimized and the time dependent diffusion of curcumin liposomes was performed ex vivo. The ex vivo diffusion study shows promising results about penetration power of curcumin liposomes. The presentation will focus mainly on the formulation, characterization of the curcumin liposomes and its anticancer potential in monolayer versus spheroid culture system.