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.
Papagiannaros
Aristarchos
A
Department of Pharmaceutical Technology, School of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Zografou Athens, Greece.
Dimas
Kostas
K
Papaioannou
George Th
GT
Demetzos
Costas
C
D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D050091:Dendrimers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004355:Drug Stability; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D050091:Dendrimers; D008081:Liposomes; D011073:Polyamines; D004317:Doxorubicin