Development and characterization of magnetic cationic liposomes for targeting tumor microvasculature.
Cationic liposomes preferentially target tumor vasculature compared to vessels in normal tissues. The distribution of cationic liposomes along vascular networks is, however, patchy and heterogeneous. To target vessels more uniformly we combined the electrostatic properties of cationic liposomes with the strength of an external magnet. We report part I of development. We evaluated bilayer physical properties of our preparations. We investigated interaction of liposomes with target cells including the role of PEG (polyethylene-glycol), and determined whether magnetic cationic liposomes can respond to an external magnetic field. The inclusion of relatively high concentration of MAG-C (magnetite) at 2.5 mg/ml significantly increased the size of cationic liposomes from 105+/-26.64 to 267+/-27.43 nm and reduced the zeta potential from 64.55+/-16.68 to 39.82+/-5.26 mv. The phase transition temperature of cationic liposomes (49.97+/-1.34 degrees C) reduced with inclusion of MAG-C (46.05+/-0.21 degrees C). MAG-C cationic liposomes were internalized by melanoma (B16-F10 and HTB-72) and dermal endothelial (HMVEC-d) cells. PEG partially shielded cationic charge potential of MAG-C cationic liposomes, reduced their ability to interact with target cells in vitro, and uptake by major RES organs. Finally, application of external magnet enhanced tumor retention of magnetic cationic liposomes.
Dandamudi
Suman
S
Northeastern University, 360 Huntington Avenue, Bouvé College of Health Sciences, Department of Pharmaceutical Sciences, 110 Mugar Hall, Boston, MA 02115, USA.
Campbell
Robert B
RB
D000818:Animals; D002412:Cations; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D020405:Dermis / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007279:Injections, Subcutaneous; D008051:Lipid Bilayers; D008081:Liposomes / Q000493:pharmacokinetics / Q000494:pharmacology*; D008280:Magnetics; D008297:Male; D008545:Melanoma / Q000473:pathology; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution
D002412:Cations; D008051:Lipid Bilayers; D008081:Liposomes; D011092:Polyethylene Glycols