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

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.