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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-5-11
pubmed:abstractText
Enzymatic and physical barrier properties of anterior ocular membranes were characterized. The permeation and metabolic degradation of [D-Ala(2)]-methionine enkephalinamide (DAMEA) in the albino rabbit cornea, conjunctiva and sclera were studied in vitro. DAMEA was administered with and without peptidase inhibitors bestatin (aminopeptidase inhibitor) and SCH 39370 (enkephalinase inhibitor). The modified Ussing chambers were used to study the peptide permeation and the samples were analyzed with a novel HPLC method using UV and EC detectors. Sclera was the most permeable membrane to DAMEA, while cornea was almost impermeable to DAMEA. Without inhibitors, the permeability coefficients of DAMEA were 2. 7x10(-8) cm/s, 3.1x10(-6) cm/s and 12.5x10(-6) cm/s in the cornea, conjunctiva and sclera, respectively. DAMEA was partly metabolized to tyrosine (Tyr) and tyrosine-D-alanine-glycine (Tyr-D-Ala-Gly). When inhibitors were co-administered with DAMEA, the corneal permeability of intact DAMEA increased 15 times, while conjunctival permeability increased 5.5 times and scleral permeability remained practically unaltered. The formation of metabolites decreased markedly, when the inhibitors were used. Interestingly, when the permeability of DAMEA was compared to permeabilities of polyethylene glycols in different membranes, the permeation was in the same range suggesting that DAMEA permeates through cornea via a paracellular pathway. Both enzymatic and physical barriers were more prominent in the cornea than in the conjunctiva and sclera. Non-corneal pathway of absorption and combined with inhibition of peptidases may be the most viable pathway for ocular peptide administration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0928-0987
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
265-70
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Enzymatic and permeation barrier of [D-Ala(2)]-Met-enkephalinamide in the anterior membranes of the albino rabbit eye.
pubmed:affiliation
Department of Pharmaceutics, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland. kaisa.hamalainen@orion.fi
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't