Prolonging the in vivo residence time of prostaglandin E1 with biodegradable nanoparticles

Tsutomu Ishihara, Miyuki Takahashi, Megumu Higaki, Mitsuko Takenaga, Tohru Mizushima, Yutaka Mizushima

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Purpose. Prostaglandins have potent and diverse biologic activities, but their clinical application is severely restricted, mainly due to rapid inactivation in vivo. In order to modulate the pharmacokinetics of prostaglandin E1 (PGE1), we prepared biodegradable nanoparticles as a drug carrier. Methods. Nanoparticles encapsulating PGE1 were prepared from a blend of poly(lactic acid) homopolymer and poly(ethylene glycol)-poly(lactide) block copolymer by the solvent diffusion method in the presence of iron. Results. PGE1 was efficiently and stably embedded in the nanoparticles through interaction with iron, despite being relatively hydrophilic and having unstable chemical properties. Depending on the isomers and molecular weight of poly(lactic acid) selected, PGE1 was gradually released from the nanoparticles at various rates into diluted serum in vitro. Both stable retention of PGE1 in the nanoparticles and coating of the nanoparticles with poly(ethylene glycol) led to an extremely extended blood residence time of PGE1, as well as preferential accumulation in vascular lesions. Conclusions. These results suggest that the present strategy is useful to advance the clinical application of PGE 1 as a therapeutic agent for vascular disorders.

Original languageEnglish
Pages (from-to)1686-1695
Number of pages10
JournalPharmaceutical research
Volume25
Issue number7
DOIs
Publication statusPublished - 2008 Jul 1

Keywords

  • Iron
  • Nanoparticle
  • Poly(lactic acid)
  • Prostaglandin E
  • Vascular disorder

ASJC Scopus subject areas

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

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  • Cite this

    Ishihara, T., Takahashi, M., Higaki, M., Takenaga, M., Mizushima, T., & Mizushima, Y. (2008). Prolonging the in vivo residence time of prostaglandin E1 with biodegradable nanoparticles. Pharmaceutical research, 25(7), 1686-1695. https://doi.org/10.1007/s11095-008-9549-8