Effect of bilayer distruption on transdermal transport of low-molecular weight hydrophobic solutes.
OBJECTIVE
Applications of transdermal drug delivery are limited by low skin permeability. Several chemicals have been used to enhance transdermal drug transport, many of which enhance skin permeability by disordering lipid bilayers. The objective of this study was to develop a mathematical model to describe the effect of bilayer disrupting agents on skin permeability to low molecular weight hydrophobic drugs.


METHODS
I predicted solute partition and diffusion coefficients in the lipid bilayers of the stratum corneum using scaled particle theory, which calculates these coefficients based on the work required to create a cavity to incorporate the solute in the lipid bilayer.


RESULTS
Model equations predicted that no significant permeability enhancement would be observed for small solutes (MW < 100). Thereafter, the enhancement, E, increases with solute cross-sectional area. The resulting equation to predict the enhancement of skin permeability is given by E = exp[alpha(r2 - 8.7)], where r is solute molecular radius in angstroms and alpha is the degree of bilayer disorder. Predictions of the model were compared with the experimental data collected from several studies.


CONCLUSIONS
The model predictions compare well with the experimental data.
Mitragotri
S
S
Department of Chemical Engineering, University of California, Santa Barbara 93106, USA. samir@engineering.ucsb.edu
D000279:Administration, Cutaneous; D000450:Aldosterone / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology; D004058:Diffusion / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D008012:Lidocaine / Q000494:pharmacology; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008970:Molecular Weight; D009284:Naphthols / Q000494:pharmacology; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D012867:Skin / Q000378:metabolism*; D012996:Solutions; D013739:Testosterone / Q000494:pharmacology
D008051:Lipid Bilayers; D009284:Naphthols; D012996:Solutions; D013739:Testosterone; D000450:Aldosterone; D008012:Lidocaine; D003345:Corticosterone