Purpose: Prostaglandin E1 (PGE1) is an effective treatment for peripheral vascular diseases. The encapsulation of PGE1 in nanoparticles for its sustained-release would improve its therapeutic effect and quality of life (QOL) of patients. Methods: In order to encapsulate PGE1 in nanoparticles prepared with a poly(lactide) homopolymer (PLA) and monomethoxy poly(ethyleneglycol)-PLA block copolymer (PEG-PLA), we synthesized a series of PGE1 phosphate derivatives and tested their efficacy. Results: Among them, PGE1 2-(phosphonooxy)ethyl ester sodium salt (C2) showed the most efficient hydrolysis to yield PGE1 in human serum. An in vitro platelet aggregation assay showed that C2 inhibited aggregation only after pre-incubation in serum, suggesting that C2 is a prodrug of PGE1. In vivo, intravenous administration of C2 caused increase in cutaneous blood flow. In the presence of zinc ions, all of the synthesized PGE1 phosphate derivatives could be encapsulated in PLA-nanoparticles. Use of l-PLA instead of d,l-PLA, and high molecular weight PLA resulted in a slower release of C2 from the nanoparticles. Conclusions: We consider that C2-encapsulated nanoparticles prepared with l-PLA and PEG-d,l-PLA have good sustained-release profile of PGE1, which is useful clinically.
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