Linked Life Data

15907593

Source:http://linkedlifedata.com/resource/pubmed/id/15907593

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2005-5-23
pubmed:abstractText
Previous permeant partitioning studies with hairless mouse skin (HMS) in the presence of several chemical skin permeation enhancers have revealed that, when such enhancers induce significant skin permeability coefficient enhancement, it is accompanied by significant enhancement in the equilibrium uptake (partitioning) of the permeant into the intercellular lipid component of the stratum corneum (SC). Particularly, it was found that the 1-alkyl-2-pyrrolidones and the 1-alkyl-2-azacycloheptanones, at aqueous solution concentrations that gave skin permeation enhancement (E) of 10 for corticosterone (CS, the permeant), enhanced the equilibrium uptake of beta-estradiol (E2beta, a surrogate permeant) from the aqueous phase into the intercellular lipids of HMS SC by a factor of 5-7. This finding raised the question of whether this uptake enhancement induced by the permeation enhancer under equilibrium conditions would be essentially the same as that determined kinetically from time-dependent permeation experiments utilizing appropriate SC membrane models and Fick's laws of diffusion to treat the data. HMS transport experiments were conducted with CS as the permeant and 1-octyl-2-pyrrolidone (OP) and 1-hexyl-2-azacyloheptanone (HAZ) as the enhancers. In treating the experimental data, a one-layer skin transport model (SC only) and a two-layer model (SC layer and the epidermis/dermis layer) were both investigated. Both the partition coefficient enhancement (E(K)) and the diffusion coefficient enhancement (E(D)) were deduced from the data treatment. The results showed that when the total transport enhancement of CS was around 11, E(K) was in the range of 6-8 and E(D) was in the range of 1.5-1.9 using both the one-layer and the two-layer models. This E(K) value was found to be in good agreement with the E2beta partition enhancement obtained directly under equilibrium conditions in previous studies. This indicates that (a) the rate-limiting domain for the transport of the lipophilic permeants across HMS and the HMS SC intercellular lipid domain probed in the equilibrium partitioning experiments are essentially the same, and (b) the total flux enhancement (E) of lipophilic permeants across HMS was driven mainly by enhancing the partitioning of the permeant into the rate-limiting domain (E(K)) and secondarily by enhancing the diffusion coefficients (E(D)) of the permeant in the domain. Comparison of the one-layer and two-layer skin model results revealed that non-steady-state transport of lipophilic compounds across HMS was better described by the two-layer model because the dermis/viable epidermis played a significant role in lipophilic permeant binding.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0378-5173
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
297
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9-21
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Model analysis of flux enhancement across hairless mouse skin induced by chemical permeation enhancers.
pubmed:affiliation
Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, University of Utah, 30 S 2000 E, Rm 213, Salt Lake City, UT 84112, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural