Local Sustained Release of Prostaglandin Ei Induces Neovascularization in Murine Hindlimb Ischemia

摘要

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 mug/kg PGE_1 solution (Group L) into the ischemic muscles; daily systemic administration of PGE_1 for 2 weeks at a total dose 100 mug/kg (Group S); and single administration of PGE_1-100 mug/kg-loaded PLGA (Group P100) into the ischemic muscles. The blood perfusion in Group P100 was higher than in Groups N, L and S (ischemiconischemic 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? vs 169? (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? (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.