Transdermal delivery enhanced by magainin pore-forming peptide.
In this study we tested the hypothesis that magainin, a peptide known to form pores in bacterial cell membranes, can increase skin permeability by disrupting stratum corneum lipid structure. We further hypothesized that magainin's enhancement requires co-administration with a surfactant chemical enhancer to increase magainin penetration into the skin. In support of these hypotheses, exposure to a known surfactant chemical enhancer, N-lauroyl sarcosine (NLS), in 50% ethanol solution increased in vitro skin permeability to fluorescein 15 fold and the combination of magainin and NLS-ethanol synergistically increased skin permeability 47 fold. In contrast, skin permeability was unaffected by exposure to magainin without co-enhancement by NLS-ethanol. Furthermore, confocal microscopy showed that magainin in the presence of NLS-ethanol penetrated deeply and extensively into stratum corneum, whereas magainin alone penetrated poorly into the skin. Additional analysis by Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry showed that NLS-ethanol disrupted stratum corneum lipid structure and that the combination of magainin and NLS-ethanol disrupted stratum corneum lipids even further. Altogether, these data suggest that NLS-ethanol increased magainin penetration into stratum corneum, which further increased stratum corneum lipid disruption and skin permeability. We believe this is the first study to demonstrate the use of a pore-forming peptide to increase skin permeability. This study also presents the novel concept of using a first chemical enhancer to increase penetration of a second chemical enhancer into the skin to synergistically increase skin permeability to a model drug.
Kim
Yeu-Chun
YC
Center for Drug Design, Development and Delivery and the Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, United States.
Ludovice
Peter J
PJ
Prausnitz
Mark R
MR
D000279:Administration, Cutaneous; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D054806:Magainins; D036641:Microscopy, Fluorescence, Multiphoton; D010539:Permeability; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D029867:Xenopus Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*
D023181:Antimicrobial Cationic Peptides; D004337:Drug Carriers; D054806:Magainins; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus