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Synthesis of prostaglandin E(1) phosphate derivatives and their encapsulation in biodegradable nanoparticles.
Pharm Res ; 26(7): 1792-800, 2009 Jul.
Article en En | MEDLINE | ID: mdl-19415470
ABSTRACT

PURPOSE:

Prostaglandin E(1) (PGE(1)) is an effective treatment for peripheral vascular diseases. The encapsulation of PGE(1) in nanoparticles for its sustained-release would improve its therapeutic effect and quality of life (QOL) of patients.

METHODS:

In order to encapsulate PGE(1) in nanoparticles prepared with a poly(lactide) homopolymer (PLA) and monomethoxy poly(ethyleneglycol)-PLA block copolymer (PEG-PLA), we synthesized a series of PGE(1) phosphate derivatives and tested their efficacy.

RESULTS:

Among them, PGE(1) 2-(phosphonooxy)ethyl ester sodium salt (C2) showed the most efficient hydrolysis to yield PGE(1) 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 PGE(1). In vivo, intravenous administration of C2 caused increase in cutaneous blood flow. In the presence of zinc ions, all of the synthesized PGE(1) 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 PGE(1), which is useful clinically.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfatos / Portadores de Fármacos / Alprostadil / Nanopartículas Aspecto: Patient_preference Límite: Animals / Humans Idioma: En Revista: Pharm Res Año: 2009 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfatos / Portadores de Fármacos / Alprostadil / Nanopartículas Aspecto: Patient_preference Límite: Animals / Humans Idioma: En Revista: Pharm Res Año: 2009 Tipo del documento: Article País de afiliación: Japón
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