Abstract
Pyrimethamine-containing microspheres and implants were prepared, from various bioresorbable polymers and copolymers derived from lactic acid enantiomers and from glycolic acid. Release patterns of the temporarily entrapped drug were examined in vitro for the various systems. The efficacy of these polymer-drug systems against Plasmodium berghei was also investigated using mouse as the model animal. Both in vitro sustained release and therapeutic efficacy depend on the drug content, the respective amounts of l- and d-repeating units in lactic acid stereocopolymers and the composition in lactic and glycolic repeating units in lactic/glycolic copolymers. For some of the pyrimethamine-containing implants, protection over a period as long as 6 months has been observed which is consistent with long-term chemoprophylaxis of rodent malaria.
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