Degradation and intrahepatic compatibility of albumin-heparin conjugate microspheres.
The in vitro degradation properties of glutaraldehyde cross-linked albumin and albumin-heparin conjugate microspheres (AMS and AHCMS respectively) were evaluated using light microscopy, turbidity measurements and heparin release determinations, showing that the microspheres are degraded by proteolytic enzymes such as trypsin, proteinase K and lysosomal enzymes. The degradation rate was inversely related to the cross-link density of the microspheres. After intrahepatic administration of AHCMS, cross-linked with 0.5% glutaraldehyde, to male Wag/Rij rats by injection into a mesenteric vein (intravenoportal: i.v.p.), the microspheres were entrapped in the hepatic vascular system. The AHCMS were entrapped within terminal portal veins predominantly at the periphery of the liver. The AHCMS were degraded by cellular enzymatic processes within 2 wk after injection, with a half life of approximately 1 d. Biocompatibility of AHCMS and adriamycin-loaded AHCMS was evaluated by histological assessment of the mitotic activity of liver parenchyma and inflammatory response, and by determination of liver damage marker enzymes during 4 wk after administration. Liver damage marker enzymes were not increased compared with controls, nor were adverse effects observed upon histological examination. There was no difference in response between empty and adriamycin-loaded AHCMS.
Cremers
H F
HF
Department of Chemical Technology, University of Twente, Enschede, The Netherlands.
Wolf
R F
RF
Blaauw
E H
EH
Schakenraad
J M
JM
Lam
K H
KH
Nieuwenhuis
P
P
Verrijk
R
R
Kwon
G
G
Bae
Y H
YH
Kim
S W
SW
D000418:Albumins / Q000138:chemical synthesis / Q000378:metabolism*; D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism*; D003432:Cross-Linking Reagents; D004317:Doxorubicin / Q000008:administration & dosage; D005976:Glutaral; D006493:Heparin / Q000138:chemical synthesis / Q000378:metabolism*; D007275:Injections, Intravenous; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008863:Microspheres; D051381:Rats
D000418:Albumins; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D004317:Doxorubicin; D006493:Heparin; D005976:Glutaral