[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.
Fan
J Z
JZ
College of Pharmacy, West China University of Medical Sciences, Chengdu.
Li
T L
TL
Pang
Q J
QJ
Guan
C T
CT
He
Y
Y
Su
K Y
KY
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