Development of a new targeted liposomal delivery system of doxorubicin modified with lymphoma cell specific antibody

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2014
Dalgıç, Ali Deniz
Three doxorubicin loaded drug carrier systems were prepared against Lymphoma diseases. The first approach was to target DXR loaded liposomal system by attaching cell specific antibodies. Non-internalizing anti-CD20 antibody was used to target Namalwa cells and internalizing anti-CD30 antibody was used to target B lymphoma cells. Targeted DXR loaded liposomes were prepared and their cytotoxicity against Lymphoma cells were compared with untargeted DXR loaded liposomes. The targeted liposome formulations were optimized to have around “92” anti-CD20 and “31” anti-CD30 antibodies per single 100 nm sized liposome (HSPC:CHOL:DSPE-PEG; 2:1:0.2). After 48 hours of incubation with Namalwa cells, anti-CD20 targeted DXR loaded liposomes caused over 87% toxicity while untargeted liposomes resulted with 19% cell death. However, anti-CD30 targeted liposomes toxicity improvement compared to untargeted liposomes was not clear due to less number of targeting moieties/cell in the study. So, this system will be further optimized. A second study was performed to investigate possible doxorubicin cytotoxicity enhancement by calcitriol pretreatment on Namalwa cells. The combinational effect of both agents was investigated firstly by treating Namalwa cells with their free form. We showed that Namalwa cells are more susceptible to DXR after 72 hours of calcitriol pretreatment. Then both agents co-loaded to liposomes and cytotoxicity compared with only doxorubicin loaded liposomes. Calcitriol and DXR co-loading to liposome, enhances cytotoxicity with in a shorter time with lower concentrations. Both modified liposomal systems prepared successfully and caused improved toxicity relative to DXR loaded liposomes.
Citation Formats
A. D. Dalgıç, “Development of a new targeted liposomal delivery system of doxorubicin modified with lymphoma cell specific antibody,” M.S. - Master of Science, Middle East Technical University, 2014.