Doxorubicin-PAMAM dendrimer complex attached to liposomes: cytotoxic studies against human cancer cell lines.

Liposomes composed of HePC:EPC:SA 10:10:0.1 (molar ratio) (1) and EPC:SA 10:0.1 (molar ratio) (2) were prepared and were used for incorporating the doxorubicin-PAMAM complex (3:1 molar ratio) (3). The doxorubicin-PAMAM complex was attached to liposomes and the incorporation efficiency was 91 and 95% for 1 and 2, respectively. The incorporation efficiency for doxorubicin into PAMAM was almost 97% while doxorubicin to PAMAM molar ratio was 3.56+/-0.04. The release rate of doxorubicin as doxorubicin-PAMAM complex from liposomes 1 and 2 and from the complex 3, was studied using buffers and 50% RPMI cell culture medium at 37 and 25 degrees C. The low release rate of doxorubicin as well as the high incorporation efficiency of doxorubicin-PAMAM complex into liposomes are considered as beneficial factors concerning the activity of doxorubicin. The cytotoxic activity of the liposomal formulation 1 incorporating doxorubicin-PAMAM complex, based on doxorubicin activity, was compared to that of 2 incorporating doxorubicin-PAMAM complex and to that of 3. The results showed that complex 1 was the most active formulation against all cancer cell lines compared to that of 2 and 3. Liposomal formulations composed of lipids and of a drug-dendrimer complex could be characterized as modulatory liposomal controlled release system (MLCRS), and could provide benefits to the delivery of drugs and modulate their release.