Enhancement of systemic delivery of met-enkephalin and leu-enkephalin eyedrops with permeation enhancers.
It was found that methionine enkephalin (Met-Enk) and leucine-enkephalin (Leu-Enk) can be delivered efficiently into the systemic circulation through the outer route in rabbits. When 50 mcl of 1% Met-Enk eyedrops without absorption enhancers were instilled into eyes, the rabbits' blood concentration rose from 92 pg/ml to 153 pg/ml in 10 min. When either of two permeation enhancers (BL-9 or Brij-78) was added at a 0.5% concentration to the ophthalmic solution, the systemic absorption of 1% Met-Enk was markedly improved. Its blood level was increased to approximately 3.4 times that without the enhancer. When the eyedrops of 0.3% Met-Enk plus 0.5% absorption enhancer were administered, the blood concentration reached higher than that reached by 1% Met-Enk without permeation enhancers. Similar results were obtained with Leu-Enk except the systemic absorption was enhanced by BL-9 and Brij-78 even further to 10-fold and 8.3-fold, respectively. These results indicate that the systemic delivery of Met-Enk and Leu-Enk through eyes, especially with the addition of permeation enhancers, is a feasible alternative route to parenteral injection.
Chiou
G C
GC
Department of Medical Pharmacology and Toxicology, Texas A&M University College of Medicine, College Station.
Shen
Z F
ZF
Zheng
Y Q
YQ
Li
B H
BH
D000042:Absorption; D000818:Animals; D004743:Enkephalin, Leucine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004744:Enkephalin, Methionine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005079:Excipients; D009883:Ophthalmic Solutions; D010539:Permeability / Q000187:drug effects; D000077423:Polidocanol; D011092:Polyethylene Glycols; D011817:Rabbits; D011863:Radioimmunoassay
D005079:Excipients; D009883:Ophthalmic Solutions; D000077423:Polidocanol; D011092:Polyethylene Glycols; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; C043444:octadecyl polyoxyethylene ether