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

Background: Although intravenous administration of prostaglandin E1 (PGE1) is commonly used in the treatment of peripheral arterial disease, it rapidly becomes inactivated in the lung. Whether local administration of sustained-release (SR) PGE1 enhances neovascularization in murine hindlimb ischemia was investigated. Methods and Results: Poly lactide-co-glycolide (PLGA) microspheres were the 4-week SR carrier of PGE1. C57BL/6 mice with unilateral hindlimb ischemia were randomly treated as follows: no treatment (Group N); single administration of 100 μg/kg PGE1 solution (Group L) into the ischemic muscles; daily systemic administration of PGE1 for 2 weeks at a total dose 100 μg/kg (Group S); and single administration of PGE1-100 μg/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