Local sustained release of prostaglandin E1 induces neovascularization in murine hindlimb ischemia

Circ J. 2009 Jul;73(7):1330-6. doi: 10.1253/circj.cj-08-0999. Epub 2009 May 13.


Background: Although intravenous administration of prostaglandin E(1) (PGE(1)) is commonly used in the treatment of peripheral arterial disease, it rapidly becomes inactivated in the lung. Whether local administration of sustained-release (SR) PGE(1) enhances neovascularization in murine hindlimb ischemia was investigated.

Methods and results: Poly lactide-co-glycolide (PLGA) microspheres were the 4-week SR carrier of PGE(1). C57BL/6 mice with unilateral hindlimb ischemia were randomly treated as follows: no treatment (Group N); single administration of 100 microg/kg PGE(1) solution (Group L) into the ischemic muscles; daily systemic administration of PGE(1) for 2 weeks at a total dose 100 microg/kg (Group S); and single administration of PGE(1)-100 microg/kg-loaded PLGA (Group P100) into the ischemic muscles. The blood perfusion in Group P100 was higher than in Groups N, L and S (ischemic/nonischemic blood perfusion ratio 88 +/-11% vs 73 +/-11% (P<0.01), 77 +/-9% (P<0.05), 79 +/-11% (P<0.05), respectively). Vascular density and alphaSMA-positive-vessel density in Group P100 were higher than in Groups N, L and S (vascular density (vessels/m(2)): 241 +/-39 vs 169 +/-49 (P<0.01), 169 +/-54 (P<0.01), 201 +/-42 (P<0.05), respectively; alphaSMA-positive-vessel density (vessels/m(2)): 34 +/-10 vs 18 +/-6 (P<0.01), 21 +/-11 (P<0.01), 22 +/-10 (P<0.01), respectively)

Conclusions: Local administration of a single dose of SR PGE(1) enhances neovascularization in mice hindlimb ischemia more efficiently than daily systemic administration.

MeSH terms

  • Alprostadil / administration & dosage*
  • Alprostadil / pharmacology*
  • Alprostadil / therapeutic use
  • Animals
  • Blood Vessels / drug effects
  • Delayed-Action Preparations
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems
  • Hindlimb / blood supply*
  • Ischemia / drug therapy*
  • Lactic Acid*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microspheres*
  • Neovascularization, Physiologic / drug effects*
  • Polyglycolic Acid*
  • Polylactic Acid-Polyglycolic Acid Copolymer


  • Delayed-Action Preparations
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Alprostadil