In vivo delivery of human alpha 1-antitrypsin gene to mouse hepatocytes by liposomes.
The pTG7101 plasmid containing the full length human alpha 1-Antitrypsin was encapsulated in large (142 +/- 15 nm of diameter) and small (54 +/- 11 nm of diameter) liposomes and administered i.v. to mice (80 ng/mouse). Control animals were treated with empty (small and large) liposomes plus free DNA and with the liposome solvent buffer. The immunohistochemical results on liver cryosections and cytophotometric analysis of hepatocyte chromophore absorbance, after peroxidase reaction, indicated that significant presence of immunoreactive human alpha 1-antitrypsin was present 7 days after mice treatment with encapsulated DNA in small liposomes but not when large liposomes were used. This effect was observed in a great number of liver parenchymal cells. These results agree with the observation that only small liposomes have easy access to hepatocytes and support the idea that small liposomes are appropriate vehicles for in vivo delivery of specific genetic material to liver parenchymal cells, with high efficiency.
Aliño
S F
SF
Dpt. Pharmacology, Faculty of Medicine and Dentistry, University of Valencia, Spain.
Bobadilla
M
M
Garcia-Sanz
M
M
Lejarreta
M
M
Unda
F
F
Hilario
E
E
D000818:Animals; D004247:DNA; D004337:Drug Carriers; D006801:Humans; D007150:Immunohistochemistry; D008081:Liposomes; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D010957:Plasmids; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage* / Q000235:genetics*
D004337:Drug Carriers; D008081:Liposomes; D000515:alpha 1-Antitrypsin; D004247:DNA