Biodegradable microspheres. VI: Lysosomal release of covalently bound antiparasitic drugs from starch microparticles.

The possibilities of using polyacryl starch microparticles as a carrier for low molecular weight drugs have been investigated. Two drugs containing primary amino groups, primaquine and trimethoprim, have been covalently coupled to the starch microparticles via tri-, tetra-, and pentapeptide spacer arms. The drug-particle complexes were prepared by coupling different drug-peptide derivatives to the particles after activation of the starch with carbonyldiimidazole. The activation process with subsequent removal of activated groups did not change the degradability of the starch microparticles. The resulting drug-carrier complexes were stable in serum, while free drugs were released in a lysosome fraction. Thus, the microparticle-peptide-drug conjugates fulfill the basic requirements for a drug carrier used to target drugs to the lysosomes (e.g., for the treatment of lysosomal parasitic diseases).