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

Abstract

Background: Although intravenous administration of prostaglandin E 1 (PGE1) is commonly used in the treat-ment 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 100μg/kg PGE1 solution (Group L) into the ischemic muscles; daily systemic administration of PGE1 for 2 weeks at a total dose 100μg/kg (Group S); and single administration of PGE1-100μg/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 aSMA-positive-vessel density in Group P100 were higher than in Groups N, L and S (vascular density (vessels/m2): 241±39 vs 169±49 (P<0.01), 169±54 (P<0.01), 201±42 (P<0.05), respectively; αSMA-positive-vessel density (vessels/m2): 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 PGEi enhances neovascularization in mice hindlimb ischemia more efficiently than daily systemic administration.