title: Prostaglandin E1 -containing nanoparticles improve walking activity in an experimental rat model of intermittent claudication.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  PGE1 could be detected in the lesion site one day after the intravenous administration of Nano-PGE1 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 .
authors.affiliation: Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ishihara
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Naoko
authors.initials: N
authors.lastname: Takasaki
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Erika
authors.initials: E
authors.lastname: Hayashi
authors.forename: Kayoko
authors.initials: K
authors.lastname: Tahara
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Takenaga
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamakawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ishihara
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kasahara
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
mesh_terms: D000527:Alprostadil / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D005080:Exercise Test; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007383:Intermittent Claudication / Q000188:drug therapy* / Q000503:physiopathology; D035002:Lower Extremity / Q000098:blood supply; D053758:Nanoparticles; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016138:Walking
chemical_list: D014665:Vasodilator Agents; D000527:Alprostadil
keywords: biodegradable nanoparticles; encapsulation; intermittent claudication; prostaglandin E1; quality of life