Vascular targeting of doxorubicin using cationic liposomes.
Tumor vessel has been recognized as an important target for anticancer therapy. Cationic liposomes have been shown to selectively target tumor endothelial cells, thus can potentially be used as a carrier for chemotherapy agents. In this study, cationic liposomes containing 20 mol% cationic lipid dimethyl dioctadecyl ammonium bromide (DDAB) and loaded with doxorubicin (DOX) were prepared and characterized. The cationic liposomal DOX showed 10.8 and 9.1 times greater cytotoxicity than control PEGylated liposomal DOX in KB oral carcinoma and L1210 murine lymphocytic leukemia cells, and 7.7- and 6.8-fold greater cytotoxicity compared to control neutral non-PEGylated liposomal DOX, repectively, in these two cell lines. Although cationic liposomal DOX had higher tumor accumulation at 30 min after intravenous administration compared to control liposomes (p<0.05), DOX uptake of these liposomes at 24h post-injection was similar to that of PEGylated liposomal DOX (p>0.05) and approximately twice the levels of the free drug and non-PEGylated liposomes. In a murine tumor model generated using L1210 cells, increased survival rate was obtained with cationic liposomal DOX treatment compared to free DOX (p<0.01), neutral liposome control (p<0.01), as well as PEGylated liposomes (p<0.05). In conclusion, the cationic liposomal DOX formulation produced superior in vitro cytotoxicity and in vivo antitumor activity, and warrants further investigation.
Wu
Jun
J
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Lee
Alice
A
Lu
Yanhui
Y
Lee
Robert J
RJ
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001692:Biological Transport; D002412:Cations; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004339:Drug Compounding; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D051379:Mice; D008811:Mice, Inbred DBA; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D002412:Cations; D008055:Lipids; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; C046112:didodecyldimethylammonium; D011092:Polyethylene Glycols; D004317:Doxorubicin