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


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 microg/kg PGE(1) solution (Group L) into the ischemic muscles; daily systemic administration of PGE(1) for 2 weeks at a total dose 100 microg/kg (Group S); and single administration of PGE(1)-100 microg/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 alphaSMA-positive-vessel density in Group P100 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; alphaSMA-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 PGE(1) enhances neovascularization in mice hindlimb ischemia more efficiently than daily systemic administration.
Esaki
Jiro
J
Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan.
Sakaguchi
Hisashi
H
Marui
Akira
A
Bir
Shyamal Chandra
SC
Arai
Yoshio
Y
Huang
Yuhong
Y
Tsubota
Hideki
H
Kanaji
Toshiya
T
Ikeda
Tadashi
T
Sakata
Ryuzo
R
D000527:Alprostadil / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000188:drug therapy*; D019344:Lactic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000527:Alprostadil