Methyl ester of prostaglandin D2 as a delivery system of prostaglandin D2 into brain

Abstract We examined the permeability of the blood-brain barrier to a methyl ester of prostaglandin D 2 and the brain uptake was assessed by radioactivity measurements and radioimmunoassay. When the methyl ester (1 mg/kg) was administered intravenously into mice, it was rapidly taken up by the brain (189 ng/g brain at 30 s) and disappeared from the brain with a half-life of 9 s, whereas it was hardly detectable in the blood. The methyl ester transported into the brain was hydrolyzed to prostaglandin D 2 and the time course of prostaglandin D 2 levels showed an accumulation phase with a peak at 30 s. The total amount of prostaglandin D 2 and its methyl ester was 279 ng/g brain at 30 s after injection, corresponding to 0.5% of the administered dose and being 6-times higher than that after prostaglandin D 2 injection. The advantage of the methyl ester over prostaglandin D 2 for brain uptake was observed at doses higher than 0.2 mg/kg, where the methyl ester which escaped from hydrolysis in the blood was taken up more effectively than prostaglandin D 2 . In in vitro experiments, the esterase activity on the methyl ester was shown to be 20-times greater in the plasma than in the brain homogenate. These results indicate that the esterification of prostaglandin D 2 may serve as a good system for the delivery of prostaglandin D 2 into the brain.