A New Therapeutic Combination for Osteosarcoma: Gemcitabine and Clofazimine Co-loaded Liposomal Formulation

Publication date: Available online 23 December 2018Source: International Journal of PharmaceuticsAuthor(s): Yagmur Caliskan, Ali Deniz Dalgic, Selin Gerekci, Ezgi A. Gulec, Aysen Tezcaner, Can Ozen, Dilek KeskinAbstractOsteosarcoma is the most common cancer in bone. Drug resistance is a challenge of current treatments that needs to be improved with novel treatment strategies. In this research, a new dual drug delivery system was developed with Gemcitabine (GEM) and Clofazimine (CLF) co-loaded liposome formulations. GEM is a well-known anticancer agent and CLF is a leprostatic and anti-inflammatory drug recently recognized as effective on cancer. GEM and CLF co-loaded liposomal formulation was achieved with compartmentalization as hydrophilic GEM being in core and lipophilic CLF sequestering in lipid-bilayer. Liposomes had high encapsulation efficiency (above 90%, GEM and above 80%, CLF). CLF release was enhanced while GEM release was slowed down in co-loaded liposomes compared to single cases. GEM/CLF co-loaded liposomes significantly enhanced cytotoxicity than GEM or CLF loaded liposomes on osteosarcoma cell line. CLF and GEM had synergistic effect (CI<1). Results of flow cytometry showed higher apoptotic cell ratio, caspase-3 activity, mitochondrial membrane depolarized cells’ ratio for GEM/CLF co-loaded liposome treatments than other liposomes. Cytotoxicity of CLF on bone cancer cells and also its synergistic effect with GEM on osteosarcoma is reported for the first ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research