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<0.01), 77 ±9% (P<0.05), 79 ±11% (P<0.05), respectively). Vascular density and αSMA-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 PGE1 enhances neovascularization in mice hindlimb ischemia more efficiently than daily systemic administration. (Circ J 2009; 73: 1330-1336)