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Drug Delivery and Translational Research

, Volume 8, Issue 1, pp 54–63 | Cite as

Enhanced transdermal delivery with less irritation by magainin pore-forming peptide with a N-lauroylsarcosine and sorbitan monolaurate mixture

  • Haerin Lee
  • Juhyun Park
  • Yeu-Chun KimEmail author
Original Article

Abstract

Transdermal drug delivery is advantageous over other conventional drug administration routes. However, it can be inefficient because of the natural barrier of the stratum corneum which is the uppermost layer of the skin. A previous study verified that the treatment of magainin pore-forming peptide with N-lauroylsarcosine (NLS) on human skin can increase skin permeability by 47-fold. However, NLS is well known as a potential skin irritant. The irritation potential of NLS is known to decrease when mixed with sorbitan monolaurate (S20). Encouraged by these results, we combined S20 with magainin-NLS to enhance transdermal drug transport with less skin irritation. In this study, nine groups with magainin and NLS:S20 mixtures at different concentrations and weight fractions were screened to maximize their synergistic effect. To quantify the efficacy to toxicity ratio of each formulation, we defined the ratio as the “enhancement ratio/irritation potential (ER/IP).” The ER was observed by Franz cell diffusion of the target drug fluorescein, and the IP was measured by the cytotoxicity of the NIH/3T3 mouse fibroblast cell line. As a result, the magainin with the NLS:S20 mixture increased the permeability of porcine skin as well as decreased the toxicity. Among the various combinations, a formulation of 2% (w/v) NLS:S20 with a weight fraction of 0.6:0.4 had the largest ER/IP. ATR-FTIR spectroscopy of the formulations and skin was done to analyze the interactions in the formulations themselves and between the formulations and the skin. Both the intercellular lipidic route and transcellular route through the stratum corneum protein were involved in the delivery of fluorescein. This study turned pore-forming peptides into an efficient and safe penetration enhancer by combining them with other chemical penetration enhancers. Moreover, this discovery could be a possible method for enabling the transdermal delivery of macromolecules.

Keywords

Transdermal delivery Pore-forming peptide Magainin Chemical penetration enhancer Surfactant Skin irritation Fourier-transform infrared spectroscopy Stratum corneum 

Notes

Acknowledgements

Porcine skin was kindly donated by the Heart Research Center of Chonnam National University.

Funding

This work was supported financially by the Ministry of Science, ICT, and Future Planning (Project No. NRF-2014M3A9E4064580); Advanced Biomass R&D Center (ABC) of the Global Frontier Project funded by the Ministry of Science, ICT, and Future Planning (NRF-2015M3A6A2074238); and the KUSTAR-KAIST Institute at KAIST.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Controlled Release Society 2017

Authors and Affiliations

  1. 1.Department of Chemical and Biomolecular EngineeringKorea Advanced Institute of Science and TechnologyDaejeonRepublic of Korea

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