Galactosyl Pentadecene Reversibly Enhances Transdermal and Topical Drug Delivery
Language English Country United States Media print-electronic
Document type Journal Article
Grant support
13-23891S
Grantová Agentura České Republiky
88615
Grantová Agentura, Univerzita Karlova
SVV260401
Univerzita Karlova v Praze
PubMed
28664316
DOI
10.1007/s11095-017-2214-3
PII: 10.1007/s11095-017-2214-3
Knihovny.cz E-resources
- Keywords
- galactoside, penetration enhancers, sugar, topical drug delivery, transdermal drug delivery,
- MeSH
- Alkenes administration & dosage chemistry MeSH
- Administration, Cutaneous MeSH
- Cidofovir MeSH
- Cytosine administration & dosage analogs & derivatives chemistry MeSH
- Epidermis metabolism MeSH
- Fibroblasts drug effects metabolism MeSH
- Galactose analogs & derivatives chemistry MeSH
- Galactosides administration & dosage chemistry MeSH
- Hydrocortisone administration & dosage chemistry MeSH
- Keratinocytes drug effects metabolism MeSH
- Skin Absorption drug effects MeSH
- Skin metabolism MeSH
- Humans MeSH
- Lipids chemistry MeSH
- Organophosphonates administration & dosage chemistry MeSH
- Permeability MeSH
- Theophylline administration & dosage chemistry MeSH
- Drug Liberation MeSH
- Water MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Alkenes MeSH
- Cidofovir MeSH
- Cytosine MeSH
- Galactose MeSH
- Galactosides MeSH
- Hydrocortisone MeSH
- Lipids MeSH
- Organophosphonates MeSH
- Theophylline MeSH
- Water MeSH
PURPOSE: To study new skin penetration/permeation enhancers based on amphiphilic galactose derivatives. METHODS: Two series of alkyl and alkenyl galactosides were synthesized and evaluated for their enhancing effect on transdermal/topical delivery of theophylline (TH), hydrocortisone (HC) and cidofovir (CDV), reversibility of their effects on transepidermal water loss (TEWL) and skin impedance, interaction with the stratum corneum using infrared spectroscopy, and cytotoxicity on keratinocytes and fibroblasts. RESULTS: Initial evaluation identified 1-(α-D-galactopyranosyl)-(2E)-pentadec-2-ene A15 as a highly potent enhancer - it increased TH and HC flux through human skin 8.5 and 5 times, respectively. Compound A15 increased the epidermal concentration of a potent antiviral CDV 7 times over that reached by control and Span 20 (an established sugar-based enhancer). Infrared spectroscopy of human stratum corneum indicated interaction of A15 with skin barrier lipids but not proteins. These effects of A15 on the skin barrier were reversible (both TEWL and skin impedance returned to baseline values within 24 h after A15 had been removed from skin). In vitro toxicity of A15 on HaCaT keratinocytes and 3T3 fibroblasts was acceptable, with IC50 values over 60 μM. CONCLUSIONS: Galactosyl pentadecene A15 is a potent enhancer with low toxicity and reversible action.
See more in PubMed
Curr Med Chem. 2005;12(19):2273-91 PubMed
J Control Release. 1999 May 20;59(2):149-61 PubMed
Pharm Res. 2017 Mar;34(3):640-653 PubMed
Int J Pharm. 2000 Jul 20;202(1-2):133-40 PubMed
Eur J Pharm Biopharm. 2007 Apr;66(1):127-34 PubMed
Biochim Biophys Acta. 2006 Jul;1758(7):923-33 PubMed
Pharm Res. 2009 Apr;26(4):811-21 PubMed
J Control Release. 2006 Jan 10;110(2):307-13 PubMed
Biochim Biophys Acta. 2008 May;1778(5):1344-55 PubMed
J Invest Dermatol. 2005 Aug;125(2):183-200 PubMed
Int J Pharm. 2013 Apr 15;447(1-2):12-21 PubMed
Eur J Pharm Sci. 2001 Sep;14(2):101-14 PubMed
Arch Dermatol. 1963 Dec;88:702-5 PubMed
J Control Release. 2011 Mar 10;150(2):164-70 PubMed
J Control Release. 2013 Jan 28;165(2):91-100 PubMed
Nat Rev Drug Discov. 2005 Nov;4(11):928-40 PubMed
J Lipid Res. 1989 Mar;30(3):323-33 PubMed
Contact Dermatitis. 1991 Aug;25(2):108-14 PubMed
Arch Dermatol. 1982 Jul;118(7):474-7 PubMed
J Lipid Res. 2013 Dec;54(12):3303-11 PubMed
Skin Pharmacol Physiol. 2009;22(1):22-30 PubMed
Int J Pharm. 2000 Aug 10;203(1-2):245-53 PubMed
Biochim Biophys Acta. 2016 Feb;1858(2):220-32 PubMed
Drug Discov Today. 2004 Aug 15;9(16):697-703 PubMed
Eur J Pharm Biopharm. 2008 Jun;69(2):597-604 PubMed
Toxicol In Vitro. 2004 Oct;18(5):725-9 PubMed
Curr Drug Deliv. 2005 Jan;2(1):23-33 PubMed
Nat Rev Drug Discov. 2004 Feb;3(2):115-24 PubMed
Pharm Res. 2006 May;23(5):912-9 PubMed
Skin Pharmacol Physiol. 2007;20(6):272-82 PubMed
J Pharm Bioallied Sci. 2012 Jan;4(1):2-9 PubMed
Pharm Res. 2014 Apr;31(4):1071-81 PubMed
Contact Dermatitis. 1999 Feb;40(2):98-103 PubMed
Biochim Biophys Acta. 2011 Mar;1811(3):129-37 PubMed
Time-Dependent Differences in the Effects of Oleic Acid and Oleyl Alcohol on the Human Skin Barrier
N-Alkylmorpholines: Potent Dermal and Transdermal Skin Permeation Enhancers
In Vitro Modeling of Skin Barrier Disruption and its Recovery by Ceramide-Based Formulations
Esters of terpene alcohols as highly potent, reversible, and low toxic skin penetration enhancers
