The effect of penetration enhancers on drug delivery through skin: A QSAR study
journal contribution
posted on 2023-06-09, 03:26 authored by Taravat Ghafourian, Parinaz Zandasrar, Hamed Hamishekar, Ali NokhodchiSkin penetration enhancers are used to allow formulation of transdermal delivery systems for drugs that are otherwise insufficiently skin-permeable. A full understanding of the mode of action could be beneficial for the design of potent enhancers and for the choice of the enhancer to be used in the topical formulation of a special drug. In this study, the structural requirements of penetration enhancers have been investigated using the Quantitative Structurea-Activity Relationship (QSAR) technique. Activities of naturally occurring terpenes, pyrrolidinone and N-acetylprolinate derivatives on the skin penetration of 5-fluorouracil, diclofenac sodium (DFS), hydrocortisone (HC), estradiol and benazepril have been considered. The resulting QSARs indicated that for 5-fluorouracil and diclofenac sodium, less hydrophobic enhancers were the most active. More precisely, molecular descriptors in the corresponding QSARs indicated the possible involvement of intermolecular electron donor-acceptor interactions. This was in contrast to the skin permeation promotion of hydrocortisone, estradiol and benazepril by enhancers, where a linear relationship between enhancement activity and n-octanol/water partition coefficients of enhancers was evident. The possible mechanisms of penetration enhancement as suggested by the QSARs will be discussed. © 2004 Elsevier B.V. All rights reserved.
History
Publication status
- Published
File Version
- Accepted version
Journal
Journal of Controlled ReleaseISSN
0168-3659Publisher
ElsevierExternal DOI
Issue
1Volume
99Page range
113-125Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-11-30First Open Access (FOA) Date
2017-11-30First Compliant Deposit (FCD) Date
2017-11-30Usage metrics
Categories
No categories selectedKeywords
Intermolecular interactions; Penetration rate; Skin permeationDerivatives; Drug dosage; Drug interactions; Hydrophobicity; Molecular dynamicsSkin2 pyrrolidone derivative; 3 carene; ascaridole; benazepril; bisabolol; carveol; cineole; cymene; diclofenac; drug vehicle; estradiol; farnesol; fluorouracil; geraniol; hydrocortisone; menthol; menthone; n acetylprolinate derivative; nerolidol; octanol; phytol; piperitone; proline derivative; pulegone; pyrrolidine derivative; terpinen 4 ol; terpineol; thymol; unclassified drug; unindexed drug; verbenonearticle; controlled study; drug delivery system; drug formulary; drug penetration; drug structure; electron; human; human tissue; partition coefficient; priority journal; quantitative structure activity relation; skin penetration; skin permeabilityAdministrationCutaneous; Animals; Benzazepines; Diclofenac; Estradiol; Fluorouracil; Humans; Hydrocortisone; Mice; MiceInbred HRS; Molecular Structure; Proline; Pyrrolidinones; Skin Absorption; Structure-Activity Relationship; Terpenes
Licence
Exports
RefWorksRefWorks
BibTeXBibTeX
Ref. managerRef. manager
EndnoteEndnote
DataCiteDataCite
NLMNLM
DCDC