Synthesis of prostaglandin E1 phosphate derivatives and their encapsulation in biodegradable nanoparticles

Miho Takeda, Taishi Maeda, Tsutomu Ishihara, Haruka Sakamoto, Kanae Yuki, Naoko Takasaki, Fumihiro Nishimura, Takeshi Yamashita, Ken Ichiro Tanaka, Mitsuko Takenaga, Rie Igarashi, Megumu Higaki, Naoki Yamakawa, Yoshinari Okamoto, Hisao Ogawa, Masami Otsuka, Yutaka Mizushima, Tohru Mizushima

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1792-1800
Number of pages9
JournalPharmaceutical Research
Volume26
Issue number7
DOIs
Publication statusPublished - 2009 Jul
Externally publishedYes

Fingerprint

Alprostadil
Encapsulation
Nanoparticles
Phosphates
Derivatives
Agglomeration
Peripheral Vascular Diseases
Prodrugs
Therapeutic Uses
Platelets
Homopolymerization
Serum
Platelet Aggregation
Intravenous Administration
Zinc
Hydrolysis
Assays
Esters
Blood
Salts

Keywords

  • Biodegradable nanoparticles
  • Encapsulation
  • Prostaglandin E
  • Zinc

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Organic Chemistry
  • Molecular Medicine
  • Pharmacology (medical)
  • Biotechnology
  • Pharmacology

Cite this

Takeda, M., Maeda, T., Ishihara, T., Sakamoto, H., Yuki, K., Takasaki, N., ... Mizushima, T. (2009). Synthesis of prostaglandin E1 phosphate derivatives and their encapsulation in biodegradable nanoparticles. Pharmaceutical Research, 26(7), 1792-1800. https://doi.org/10.1007/s11095-009-9891-5

Synthesis of prostaglandin E1 phosphate derivatives and their encapsulation in biodegradable nanoparticles. / Takeda, Miho; Maeda, Taishi; Ishihara, Tsutomu; Sakamoto, Haruka; Yuki, Kanae; Takasaki, Naoko; Nishimura, Fumihiro; Yamashita, Takeshi; Tanaka, Ken Ichiro; Takenaga, Mitsuko; Igarashi, Rie; Higaki, Megumu; Yamakawa, Naoki; Okamoto, Yoshinari; Ogawa, Hisao; Otsuka, Masami; Mizushima, Yutaka; Mizushima, Tohru.

In: Pharmaceutical Research, Vol. 26, No. 7, 07.2009, p. 1792-1800.

Research output: Contribution to journalArticle

Takeda, M, Maeda, T, Ishihara, T, Sakamoto, H, Yuki, K, Takasaki, N, Nishimura, F, Yamashita, T, Tanaka, KI, Takenaga, M, Igarashi, R, Higaki, M, Yamakawa, N, Okamoto, Y, Ogawa, H, Otsuka, M, Mizushima, Y & Mizushima, T 2009, 'Synthesis of prostaglandin E1 phosphate derivatives and their encapsulation in biodegradable nanoparticles', Pharmaceutical Research, vol. 26, no. 7, pp. 1792-1800. https://doi.org/10.1007/s11095-009-9891-5
Takeda, Miho ; Maeda, Taishi ; Ishihara, Tsutomu ; Sakamoto, Haruka ; Yuki, Kanae ; Takasaki, Naoko ; Nishimura, Fumihiro ; Yamashita, Takeshi ; Tanaka, Ken Ichiro ; Takenaga, Mitsuko ; Igarashi, Rie ; Higaki, Megumu ; Yamakawa, Naoki ; Okamoto, Yoshinari ; Ogawa, Hisao ; Otsuka, Masami ; Mizushima, Yutaka ; Mizushima, Tohru. / Synthesis of prostaglandin E1 phosphate derivatives and their encapsulation in biodegradable nanoparticles. In: Pharmaceutical Research. 2009 ; Vol. 26, No. 7. pp. 1792-1800.
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AU - Maeda, Taishi

AU - Ishihara, Tsutomu

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AU - Yuki, Kanae

AU - Takasaki, Naoko

AU - Nishimura, Fumihiro

AU - Yamashita, Takeshi

AU - Tanaka, Ken Ichiro

AU - Takenaga, Mitsuko

AU - Igarashi, Rie

AU - Higaki, Megumu

AU - Yamakawa, Naoki

AU - Okamoto, Yoshinari

AU - Ogawa, Hisao

AU - Otsuka, Masami

AU - Mizushima, Yutaka

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