Sustained release of an antimalarial drug using a copolymer of glycolic/lactic acid

Abstract

A copolymer of d1-lactic acid and glycolic acid (25% and 75% by weight, respectively) was evaluated as an implantable controlled release delivery system for the antimalarial drug 2, 4-diamino-6-(2-napthylsulfonyl)-quinazoline (WR-158122). Two preparations of drug/polymer (16.7% and 33.3% drug by weight) were spray dried from common solvent systems into finely divided particles of less than 125 microns size. Suspensions in carboxymethyl cellulose of each preparation were injected in the scapular region of mice and were evaluated for efficacy against the rodent malaria Plasmodium berghei by repeated infective challenges and by the Rane antimalarial drug screening system. Duration of release was studied by measurement of trace radioactivity from the drug excreted into urine and feces. In the challenge test, several dosages of the implanted drug/polymer material and antimalarial activity over a prolonged period of time; parasitemia was not detected for several weeks and some animals survived through 14 weeks of weekly challenges, whereas all mice in control groups became malarious and survived only an average of 12 days after infection. Both preparations were effective in the Rane drug screening system; the curative dose as drug was calculated to be approximately 50 mg/kg body weight for each preparation. Recovery of excreted radioactivity indicated a sustained release through 14 weeks and residual activities at the implant sites were 2% and 13% for the 16.7% and 33.3% drug/polymer preparations, respectively. Based on these results, it is anticipated that delivery systems of this type can be developed for eventual testing against human malaria.