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Biodegradable microspheres. VII: Alterations in mouse liver morphology after intravenous administration of polyacryl
1Department of Pharmaceutical Biochemistry, University of Uppsala, Sweden.
Abstract:
Semisynthetic polyacryl starch microparticles are being investigated as drug carriers. In the present paper the possible adverse effects, reflected as morphological alterations, of iv administration of polyacryl starch microparticles were studied in mice. The spleen, lungs, and kidneys displayed a normal morphology after microparticle administration, while dose-dependent reversible alterations of the liver morphology were observed. The alterations initially consisted of vacuolization of the hepatocytes along the sinusoids, followed by unicellular hepatocyte necrosis and formation of granulomas. Later, an increased number of mitotic cells reflected tissue generation and, after two weeks, the tissue morphology was essentially normalized, with the exception of an increased number of binucleated hepatocytes. After repeated administration of the particles in low doses, the same types of alterations were observed but the kinetics of tissue repair was slower. Possible mechanisms inducing these alterations are discussed and comparisons are made with the effects of synthetic polyacrylamide microparticles.
Insights
Polyacryl starch microparticles, used as drug carriers, caused reversible liver damage in mice. While spleen, lungs, and kidneys remained unaffected, liver tissue showed dose-dependent alterations and eventual normalization.
Area of Science:
- Biomaterials Science
- Toxicology
- Drug Delivery Systems
Background:
- Semisynthetic polyacryl starch microparticles are explored for drug delivery.
- Understanding potential adverse effects of these microparticles is crucial for their clinical application.
Purpose of the Study:
- To investigate the morphological alterations in mice following intravenous administration of polyacryl starch microparticles.
- To assess the dose-dependency and reversibility of these observed changes.
Main Methods:
- Intravenous administration of polyacryl starch microparticles to mice.
- Histopathological examination of spleen, lungs, kidneys, and liver tissues.
- Evaluation of dose-dependent and time-course effects on tissue morphology.
Main Results:
- Spleen, lungs, and kidneys showed normal morphology post-administration.
- Liver morphology exhibited dose-dependent, reversible alterations including hepatocyte vacuolization, necrosis, and granuloma formation.
- Tissue regeneration was observed, with near-normalization within two weeks, though binucleated hepatocytes persisted.
Conclusions:
- Polyacryl starch microparticles can induce reversible hepatic alterations in mice.
- The observed liver changes suggest a potential toxicological profile that warrants further investigation for drug delivery applications.
- Comparison with polyacrylamide microparticles may offer insights into material-specific toxic effects.
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