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. C5713L/6 mice with unilateral hindlimb ischemia were randomly treated as follows: no treatment (Group N); single administration of 100 mu g/kg PGE1 solution (Group L) into the ischemic muscles; daily systemic administration of PGE1 for 2 weeks at a total dose 100 mu g/kg (Group S); and single administration of PGE1-100 mu g/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 alpha SMA-positive-vessel density in Group P 100 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; aSMA-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 PGE1 enhances neovascularization in mice hindlimb ischemia more efficiently than daily systemic administration. (Circ J 2009; 73: 1330-1336)