A new therapeutic combination for osteosarcoma: Gemcitabine and Clofazimine co-loaded liposomal formulation

Caliskan, Yagmur
Dalgıç, Ali Deniz
Gerekci, Selin
Gulec, Ezgi A.
Tezcaner, Ayşen
Özen, Can
Keskin, Dilek
Osteosarcoma 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 coloaded 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 time with this study. CLF's loading with GEM into liposome was also a new approach for enhancement of anticancer effect on Saos-2 cells. Therefore, GEM/CLF co-loaded liposomal delivery system is proposed as a novel approach for treatment of osteosarcoma.


Synergistic Effect of Gemcitabine and Clofazimine in Co-loaded Liposomal Formulation for Multidrug Treatment Approach of Osteosarcoma
Çalışkan, Yağmur; Güleç, Ezgi; Gerekçi, Selin; Tezcaner, Ayşen; Özen, Can; Keskin, Dilek (2017-07-19)
ntroduction: Osteosarcoma is the most common cancer in bone with high occurrence in children. The development of resistance is a challenge of current treatment strategies that needs to be improved with novel treatment strategies. In the current research, a new dual drug delivery system was developed with Gemcitabine (GEM) and Clofazimine (CLF) co-loaded liposome formulations for osteosarcoma treatment. GEM is a pyrimidine antimetabolite that inhibits DNA synthesis and CLF is a leprostatic and anti-inflammat...
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Citation Formats
Y. Caliskan et al., “A new therapeutic combination for osteosarcoma: Gemcitabine and Clofazimine co-loaded liposomal formulation,” INTERNATIONAL JOURNAL OF PHARMACEUTICS, pp. 97–104, 2019, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/30308.