Prostaglandin E1-containing nanoparticles improve walking activity in an experimental rat model of intermittent claudication

Tomoaki Ishihara, Yasunobu Yamashita, Naoko Takasaki, Shuhei Yamamoto, Erika Hayashi, Kayoko Tahara, Mitsuko Takenaga, Naoki Yamakawa, Tsutomu Ishihara, Tadashi Kasahara, Tohru Mizushima

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2 Citations (Scopus)

Abstract

Objectives Due to the low stability of lipid emulsions, a lipid emulsion of prostaglandin E1 (Lipo-PGE1) necessitates daily intravenous drip infusions. To overcome this issue, we developed nanoparticles containing PGE1 (Nano-PGE1). Nano-PGE1 showed a good sustained-release profile of PGE1 from the nanoparticles in vitro, which may permit a longer-lasting therapeutic effect to be achieved. We here examined the pharmacological activity of Nano-PGE1 in a rat experimental model of intermittent claudication induced by femoral artery ligation. Methods The walking activity of the rat was tested on a rodent treadmill. Tissue levels of PGE1 were determined by enzyme immunoassay, and skeletal muscle angiogenesis (capillary growth) was monitored by immunohistochemical analysis. Key findings PGE1 could be detected in the lesion site one day after the intravenous administration of Nano-PGE 1 but not of Lipo-PGE1. An increased accumulation of Nano-PGE1 in the lesion site compared with control (unlesioned) site was also observed. The ligation procedure reduced the walking activity, which in turn was improved by a single administration of Nano-PGE1 but not of Lipo-PGE1. The single administration of Nano-PGE1 also stimulated angiogenesis in the skeletal muscle around the ligated artery. Conclusions The findings of this study suggest that Nano-PGE1 improves the walking activity of femoral artery-ligated rats through the accumulation and sustained release of PGE1.

Original languageEnglish
Pages (from-to)1187-1194
Number of pages8
JournalJournal of Pharmacy and Pharmacology
Volume65
Issue number8
DOIs
Publication statusPublished - 2013 Aug 1

Keywords

  • biodegradable nanoparticles
  • encapsulation
  • intermittent claudication
  • prostaglandin E
  • quality of life

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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    Ishihara, T., Yamashita, Y., Takasaki, N., Yamamoto, S., Hayashi, E., Tahara, K., Takenaga, M., Yamakawa, N., Ishihara, T., Kasahara, T., & Mizushima, T. (2013). Prostaglandin E1-containing nanoparticles improve walking activity in an experimental rat model of intermittent claudication. Journal of Pharmacy and Pharmacology, 65(8), 1187-1194. https://doi.org/10.1111/jphp.12080