Short-Chain Ceramides for Enhancing Cytotoxicity of Liposome-Encapsulated Doxorubicin Toward Human Breast Cancer (MDA-MB-231) and Prostate Cancer (PC-3) Cells
Type of DegreeMaster's Thesis
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Co-delivery of short chain ceramide, C6-Ceramide (C6-Cer) and C8-Ceramide (C8-Cer) and doxorubicin (DOX) using a liposomal system in MDA-MB-231 breast cancer and PC3 prostate cancer cell lines for synergistic cytotoxic effects was investigated. Liposomes, containing disparate ceramides, were prepared in a molar ratio of 44:40:4:12 mol% of DOTAP/ cholesterol/PEG2000-DSPE/Ceramide, respectively using lipid film hydration method and loaded with doxorubicin (ratio of 0.2:1). Liposomes were characterized by measuring size, polydispersity index, release profile and doxorubicin content. In addition, in vitro cytotoxicity and cellular uptake were evaluated. Doxorubicin liposomes enriched with either C6 or C8 ceramide exhibited high drug encapsulation efficiency (>90%) and small size (~ 94 nm). Enhanced cytotoxic effect was noticed between doxorubicin and both C6 and C8 ceramide in both cell lines. Doxorubicin enriched with C6 and C8-ceramide exhibited the highest cytotoxicity against MDA-MB-231 and PC3 cells compared to liposome formulation that does not contain ceramide and free doxorubicin. Furthermore, cellular uptake of liposomal doxorubicin enriched with C6 and C8-ceramide was higher than both free doxorubicin and liposome formulation without ceramide.