In vivo and electron microscopic studies of rat liver after intravenous injection of polyamino acid microspheres.
In vivo and electron microscopy were used to study the hepatocellular responses of rat livers to intravenously injected polymeric microspheres. Two microsphere preparations with different surface characteristics and degradability were used in this study. In vivo microscopy revealed that both poly(benzyl L-glutamate) (PBLG) and poly(hydroxypropyl L-glutamine) (PHPG) microspheres caused disturbance in the microcirculation of rat liver up to 2 months after injection. The observed changes included stagnant flow and adherence of white blood cells to the endothelial lining of venules an sinusoids. Kupffer cell (KC) activation following phagocytosis of microspheres was evidenced by the enlargement of KCs and increased number of KCs taking up fluorescent latex particles. Electron microscopy of rat livers revealed a wide range of hepatocellular injury associated with the administration of PBLG and PHPG microspheres. These results indicate that a small amount of remaining microspheres is sufficient to induce continuous disturbance to hepatic microcirculation and that particulate drug carriers should be designed to be rapidly degraded so that the return to normal liver function is possible.
Li
C
C
Division of Diagnostic Imaging, University of Texas M. D. Anderson Cancer Center, Houston 77030.
McCuskey
P
P
Kan
Z
Z
Yang
D J
DJ
Wright
K C
KC
Wallace
S
S
D000818:Animals; D005453:Fluorescence; D007275:Injections, Intravenous; D007728:Kupffer Cells / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000648:ultrastructure*; D008102:Liver Circulation / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects; D008854:Microscopy, Electron; D008863:Microspheres; D010455:Peptides / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D010455:Peptides; C003172:poly-gamma-benzyl-L-glutamate; D011099:Polyglutamic Acid; C008966:poly-N(5)-(3-hydroxypropyl)-1-glutamine