Biodegradable Microspheres IV: Factors Affecting the Distribution and Degradation of Polyacryl Starch Microparticles

Polyacryl starch microparticles have been suggested as lysosomotropic drug carriers. In this paper we report the study of the distribution and elimination of polyacryl starch microparticles after intravenous administration in mice. The half-life of the particles in the circulation is short (< 5 min) and they are efficiently taken up by the reticuloendothelial (RES) system, mainly in the liver (50–90%). The stability of the particles, as studied both in vitro (with serum and lysosome preparations) and in vivo (via the elimination from the liver), depends on two factors, the amount of initiator of the polymerization process (N,N,N',N',N'-tetramethylethylenediamine, TEMED) and the degree of derivatization of the starch. TEMED, used for the polymerization of the acryl groups forming the hydrocarbon chains, determines the number and the length of the cross-links between the starch molecules. The results indicate that large amounts of TEMED induce the formation of particles with many and short cross-links, which are easily degraded and dissolved in serum and more rapidly eliminated from the liver. The stability in serum can be improved by coadministration of soluble starch. Prolonged treatment of the starch with acrylic acid glycidyl ester leads to a high degree of derivatization and, consequently, to less degradable particles remaining in the lysosomes of the RES. The extent of biodegradation of the polyacryl starch particles could be anticipated from in vitro degradation of the monomers (acryloylated starch) with amyloglucosidase.