The lacZ gene transfer into L929 cells and [14C]-DNA tissue distribution following intraperitoneal administration of new pH-sensitive lipoplexes in mice.
The efficacy of lacZ gene transfer into the L929 cell line and a local [l4C]-DNA delivery in male NMRI mice (10-12 weeks old), were studied using new pH-sensitive liposomes, containing phosphatidylcholine/glycyrrhizin (PC/GL) or alpha-tocopherol ester of succinic acid (PC/TSA). The reporter gene (pQE-LacZ plasmid) was transferred into L929 cells using corresponding lipoplexes, 0.5% of cells being transfected. Tissue distribution of Gasserian ganglion neurinoma cell [14C]-DNA fragments and corresponding PC/GL and PC/TSA lipoplexes, were examined following intraperitoneal administration of a 24 h postdose. The [14C]-DNA itself was not detected in any organs at a 1.5 h postdose. The use of PC/GL or PC/TSA lipoplexes considerably changed the biodistribution of [14C]-DNA in mice tissues. The maximal content of [14C]-DNA for both types of lipoplexes was observed in the intestine (50% dose equiv./g) and the spleen (30% dose equiv./g). The content of [14C]-DNA in liver and kidneys was equal to 4 and 10% for liver and kidneys in the case of PC/GL-lipoplexes, and 15 and 6%, for PC/TSA, respectively. Thus, the tropicity for PC/GL-lipoplexes to liver was not detected under i.p. administration.
Sviridov
Y V
YV
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow.
Zhdanov
R I
RI
Podobed
O V
OV
Tsvetkova
T A
TA
Konstantinov
I
I
Bogdanenko
E V
EV
D000818:Animals; D002250:Carbon Radioisotopes; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019695:Glycyrrhizic Acid; D006863:Hydrogen-Ion Concentration; D007274:Injections, Intraperitoneal; D007763:Lac Operon / Q000235:genetics*; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D009928:Organ Specificity; D011849:Radioactive Tracers; D014018:Tissue Distribution; D024505:Tocopherols; D014162:Transfection / Q000379:methods / Q000592:standards*; D014810:Vitamin E / Q000031:analogs & derivatives*
D002250:Carbon Radioisotopes; D008081:Liposomes; D011849:Radioactive Tracers; D014810:Vitamin E; D019695:Glycyrrhizic Acid; D004247:DNA; D024505:Tocopherols