Biodegradable microspheres. VII: Alterations in mouse liver morphology after intravenous administration of polyacryl starch microparticles with different biodegradability.

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.