Transdermal delivery enhancement with less irritation by magainin pore-forming peptide with N-lauroylsarcosine and sorbitan monolaurate mixture

Abstract

Transdermal drug delivery is advantageous over other conventional drug administration routes. However, it can be inefficient because of the natural barrier of stratum corneum, the uppermost layer of the skin. Previous study verified that the treatment of magainin pore-forming peptide with N-lauroyl sarcosine (NLS) to human skin can increase skin permeability by 47-fold. However, NLS is well known for its skin irritation potential. Irritation potential of NLS is known to be decreased when mixed with sorbitan monolaurate (S20). Encouraged by these results, we combined S20 with magainin-NLS to enhance the transdermal drug transport with less skin irritation. In this study, nine groups having magainin with NLS:S20 mixture in different concentrations and weight fractions were screened to maximize the synergy. To quantify each formulation’s potency to toxicity, we defined the ratio as ‘enhancement ratio/irritation potential (ER/IP)’. ER was observed by Franz cell diffusion of target drug fluorescein, and IP was measured by cytotoxicity of NIH/3T3 mouse fibroblast cell line. In this study, the magainin with NLS:S20 mixture appeared to increase the permeability along with the decrease in toxicity. Among combinations, formulation with 2% (w/v) NLS:S20 in weight fraction of 0.6:0.4 showed the largest ER/IP. ATR-FTIR spectroscopy of formulations and skin was collected to analyze the interactions in formulation itself, and between formulation and skin. Both intercellular lipidic route and transcellular route through SC protein was involved in the fluorescein delivery. This study makes the pore-forming peptides as efficient and safe penetration enhancer when combined with other chemical penetration enhancers. Moreover, this discovery presents as one of the possible solutions allowing the transdermal delivery of macromolecules.