Synergistic enhancement of skin permeability by N-lauroylsarcosine and ethanol.
To develop formulations for transdermal drug delivery, this study tested the hypothesis that the anionic surfactant, N-lauroylsarcosine (NLS), and ethanol synergistically increase skin permeability by increasing the fluidity of stratum corneum lipid structure. Skin permeability experiments showed that transdermal delivery of fluorescein across human cadaver epidermis was increased by up to 47-fold using formulations containing NLS in aqueous ethanol solutions. Skin permeability was increased by increasing NLS concentration in combination with 25-50% ethanol solutions. Skin permeability was shown to correlate with skin electrical conductivity measurements, changes in differential scanning calorimetry lipid transition peak temperature, and Fourier transform infrared spectroscopy CH stretching peak shifts indicative of stratum corneum lipid fluidization and changes in protein conformation. Evidence for lipid extraction was also evident, but did not appear to be responsible for the observed increases in skin permeability. We conclude that NLS in aqueous ethanol formulations can dramatically increase skin permeability by a mechanism involving synergistic lipid-fluidization activity in the stratum corneum.
Kim
Yeu-Chun
YC
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0100, USA.
Park
Jung-Hwan
JH
Ludovice
Peter J
PJ
Prausnitz
Mark R
MR
D000279:Administration, Cutaneous; D002102:Cadaver; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D017097:Electric Impedance; D000431:Ethanol / Q000494:pharmacology*; D019793:Fluorescein / Q000008:administration & dosage / Q000378:metabolism; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry; D010539:Permeability; D011487:Protein Conformation; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents / Q000494:pharmacology*; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
D005456:Fluorescent Dyes; D008055:Lipids; D013501:Surface-Active Agents; D000431:Ethanol; C025231:sarkosyl; D019793:Fluorescein; D012521:Sarcosine