[Preparation of hepatic targeting antivirus agent NGA-ACV and its targeting property].
Neoglycoalbumin (NGA), a special ligend of asialoglycoprotein receptor on the hepatocyte, was linked via a butanediacyl bridge to acyclovir to form a conjugate NGA-ACV. By using DTA (Differential thermoanalysis) and HPLC analysis, ACV was shown to be connected with NGA by covalent bonds and stable in blood. The radio-biodistribution of 131I-NGA-ACV with high drug density in vivo was carried out in mice. The maximum absorption of 131I-NGA-ACV in liver was 81.7 +/- 10.4% at 5 min. The radioimage of 131I-NGA-ACV with high or low drug density in rabbit showed no significant difference in liver targeting property. The competitive connection tests indicated that 131I-NGA-ACV was concentrated in liver through receptor mediated mechanism. A tentative test of antihepatitis B of NGA-ACV and ACV in vitro showed that the effective dose of the former was significantly lower than that of the latter.
College of Pharmacy, West China University of Medical Sciences, Chengdu.
J Z
JZ
Fan
T L
TL
Li
Q J
QJ
Pang
C T
CT
Guan
Y
Y
He
K Y
KY
Su
D000212:Acyclovir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000418:Albumins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001667:Binding, Competitive; D005260:Female; D000922:Immunotoxins / Q000493:pharmacokinetics*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D051379:Mice; D011817:Rabbits; D011877:Radionuclide Imaging; D011897:Random Allocation; D014018:Tissue Distribution
D000418:Albumins; D000998:Antiviral Agents; D000922:Immunotoxins; C064861:galactosyl-neoglycoalbumin; D000212:Acyclovir