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Biodegradable microspheres. IV: Factors affecting the distribution and degradation of polyacryl starch microparticles
Abstract:
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 (less than 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'-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.
Insights
Polyacryl starch microparticles are rapidly cleared from circulation by the reticuloendothelial system, primarily the liver. Particle stability and elimination depend on polymerization initiator levels and starch derivatization.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Nanotechnology
Background:
- Polyacryl starch microparticles are investigated as potential lysosomotropic drug carriers.
- Understanding their in vivo behavior is crucial for drug delivery applications.
Purpose of the Study:
- To investigate the distribution and elimination of polyacryl starch microparticles after intravenous administration in mice.
- To determine factors influencing the stability and degradation of these microparticles.
Main Methods:
- Intravenous administration of polyacryl starch microparticles in mice.
- In vitro stability studies using serum and lysosome preparations.
- In vivo pharmacokinetic analysis and liver uptake quantification.
- Assessment of particle degradation influenced by N,N,N',N'-tetramethylethylenediamine (TEMED) and degree of starch derivatization.
Main Results:
- Microparticles exhibited a short half-life (<5 min) in circulation.
- Efficient uptake by the reticuloendothelial system (RES), predominantly in the liver (50-90%).
- Particle stability was modulated by TEMED concentration and starch derivatization degree.
- High TEMED levels led to less stable, rapidly cleared particles, while increased derivatization enhanced stability.
Conclusions:
- Polyacryl starch microparticle clearance is rapid, with significant hepatic accumulation.
- Particle stability and degradation kinetics are controllable via synthesis parameters (TEMED, derivatization).
- Biodegradation can be predicted using in vitro amyloglucosidase assays on acryloylated starch.