Inhibitory effect of prostaglandin E1 on laurate-induced peripheral vascular occlusive sequelae in rabbits: optimized topical formulation with beta-cyclodextrin derivative and penetration enhancer HPE-101.
Prostaglandin E1 (PGE1) and its inclusion complexes with beta-cyclodextrin (beta-CyD) and O-carboxymethyl-O-ethyl-beta-cyclodextrin (CME-beta-CyD) were made as topical preparations. The PGE1 preparations, when applied with a penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentane-2-one (HPE-101), markedly increased the regional blood flow in the ear of rabbits and were longer acting than when administered by the intravenous route. Topical application of the PGE1 preparations significantly protected rabbits against laurate-induced peripheral vascular occlusive sequelae; the protective potency increased in the order of PGE1 alone = beta-CyD complex < CME-beta-CyD complex preparation. The PGE1 preparations elicited skin reactions such as erythema and oedema depending on their vasodilating actions. These reactions disappeared gradually after removal of the preparations, and hence may not be serious obstacles for their safe use. These results suggest that combinations of CME-beta-CyD and HPE-101 work synergistically to facilitate the entry of PGE1 into the skin, and consequently enhance the therapeutic potential of PGE1 in the topical preparation tested.
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
H
H
Adachi
T
T
Irie
K
K
Uekama
T
T
Manako
T
T
Yano
M
M
Saita
D000287:Administration, Topical; D000527:Alprostadil / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D003505:Cyclodextrins / Q000494:pharmacology*; D004337:Drug Carriers; D004338:Drug Combinations; D004423:Ear / Q000098:blood supply*; D007850:Lauric Acids / Q000633:toxicity; D008297:Male; D009824:Ointments; D016491:Peripheral Vascular Diseases / Q000139:chemically induced / Q000188:drug therapy*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits
D003505:Cyclodextrins; D004337:Drug Carriers; D004338:Drug Combinations; D007850:Lauric Acids; D009824:Ointments; D011758:Pyrroles; C030358:lauric acid; C075725:1-(2-(decylthio)ethyl)azacyclopentane-2-one; D000527:Alprostadil