Role of Corneocytes in Skin Transport Revised--A Combined Computational and Experimental Approach

Purpose To investigate mechanisms of compound-corneocyte interactions in a combined experimental and theoretical approach. Materials and Methods Experimental methods are presented to investigate compound-corneocyte interactions in terms of dissolution within water of hydration and protein binding an...

Full description

Saved in:
Bibliographic Details
Published in:Pharmaceutical research 2009-06, Vol.26 (6), p.1379-1397
Main Authors: Hansen, Steffi, Naegel, Arne, Heisig, Michael, Wittum, Gabriel, Neumann, Dirk, Kostka, Karl-Heinz, Meiers, Peter, Lehr, Claus-Michael, Schaefer, Ulrich F
Format: Article
Language:English
Subjects:
Biochemistry
Biological and medical sciences
Biological Transport
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Caffeine - metabolism
Caffeine - pharmacokinetics
Cellular biology
compartmental model
dual-sorption theory
Epidermis - chemistry
Epidermis - cytology
Epidermis - metabolism
Female
Flufenamic Acid - metabolism
Flufenamic Acid - pharmacokinetics
General pharmacology
Humans
Keratins - analysis
Keratins - metabolism
Langmuir isotherm
Lipids - analysis
Medical Law
Medical sciences
Models, Biological
partition coefficient
Pharmaceutical sciences
Pharmaceutical technology. Pharmaceutical industry
Pharmacology
Pharmacology. Drug treatments
Pharmacology/Toxicology
Pharmacy
Protein Binding
Research Paper
Skin
Skin Absorption
Solubility
Testosterone - metabolism
Testosterone - pharmacokinetics
Transdermal medication
Water - analysis
Water - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Purpose To investigate mechanisms of compound-corneocyte interactions in a combined experimental and theoretical approach. Materials and Methods Experimental methods are presented to investigate compound-corneocyte interactions in terms of dissolution within water of hydration and protein binding and to quantify the extent of the concurrent mechanisms. Results are presented for three compounds: caffeine, flufenamic acid, and testosterone. Two compartmental stratum corneum models M1 and M2 are formulated based on experimentally determined input parameters describing the affinity to lipid, proteins and water. M1 features a homogeneous protein compartment and considers protein interactions only via intra-corneocyte water. In M2 the protein compartment is sub-divided into a cornified envelope compartment interacting with inter-cellular lipids and a keratin compartment interacting with water. Results For the non-protein binding caffeine the impact of the aqueous compartment on stratum corneum partitioning is overestimated but is successfully modeled after introducing a bound water fraction that is non-accessible for compound dissolution. For lipophilic, keratin binding compounds (flufenamic acid, testosterone) only M2 correctly predicts a concentration dependence of stratum corneum partition coefficients. Conclusions Lipophilic and hydrophilic compounds interact with corneocytes. Interactions of lipophilic compounds are probably confined to the corneocyte surface. Interactions with intracellular keratin may be limited by their low aqueous solubility.
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-009-9849-7