Citotoxicity and biodistribution of cationic lipopolymer/plasmidic DNA complexes

C. FACUNDO TEMPRANA; S. AMOR; A. LIS FEMIA; J. GASPARRI; S. DEL V. ALONSO

San Miguel de Tucumán

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2009

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Liposomes have been widely used as drug delivery systems. In particular, polymeric liposomes have shown interesting membrane properties and enhanced stability. The aim of this study was to evaluate cell interaction of polymeric liposomes with and without DNA complexing in vitro and in vivo. Lipopolymers were formulated with 1,2-bis(10,12-tricosadiynoyl)-Glycero-3-Phosphocholine (DC8,9PC) and 1,2-dimyristoyl--Glycero-3-Phosphocholine (DMPC) in a 1:1 molar ratio and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), octadecylamine (SA) or trimethyl(2-myristoyloxyethyl)ammonium (MCl) in a 0.2 mol ratio. Size, Z potential and cytotoxicity was evaluated for each system, complexed or not with plasmidic pDsRed2-N1 DNA. Cell interaction, transfection and biodistribution in Balb-c mice, were analized by flow cytometry. Results showed higher cell toxicity in those systems containing SA wich was reduced when complexed with DNA. Though no signifficant transfection was found for described systems, an important cell interaction was observed related to Z potential and size. Furthermore, after intravenous injection of the systems (elapsed time, one hour) lipopolymer fluorescence was found in spleen and intestines cells for DC8,9PC:DMPC:DOTAP (1:1:0,2)/pDsRed (16:1). No differences respect to control were found for DC8,9PC:DMPC:MCl (1:1:0,2)/pDsRed (16:1) complexes nor with the systems alone. In this sence cationic lipid influenced cell interaction and biodistribution of lipopolymer/DNA system.