Biodistribution of liposome/DNA systems after subcutaneous and intraperitoneal inoculation.
In this work, we analyzed protein interaction, cell toxicity, and biodistribution of liposome formulation for further possible applications as DNA vehicles in gene-therapy protocols. In relation to protein interaction, cationic liposomes showed the lowest protein interaction, but this parameter was incremented with DNA association. On the other hand, noncharged liposomes presented high protein interaction, but DNA association decreased this parameter. Protein interaction of polymeric liposomes did not change with DNA association. Cell toxicity of these three liposome formulations was low, cell death became present at concentrations higher than 0.5 mg/mL, and these concentrations were higher than those usually used in transfection assays. In the case of noncharged and polymeric liposomes, toxicity increased upon interaction with serum proteins. DNA/liposome-mediated tissue distribution was analyzed in Balb-c female mice. Results indicated that noncharged liposomes were able to deliver DNA to liver after intraperitoneal (i.p.) inoculation, while polymeric liposomes were able to deliver DNA to kidney by using the same inoculation route. Cationic liposomes were able to deliver DNA to a wide range of tissues by the i.p. route (e.g., liver, intestine, kidney, and blood). After subcutaneous inoculation, only cationic liposomes were able to deliver DNA to blood, but not the other two formulations within the detection limits of the method.
Laboratorio de Biomembranas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Bernal, Buenos Aires, Argentina. nschiara@unq.edu.ar
Nadia S
NS
Chiaramoni
Julieta
J
Gasparri
Lucía
L
Speroni
María C
MC
Taira
Silvia del Valle
Sdel V
Alonso
D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D005260:Female; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007668:Kidney / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection
D008081:Liposomes; D012710:Serum Albumin, Bovine; D004247:DNA