De Novo Design of Skin-Penetrating Peptides for Enhanced Transdermal Delivery of Peptide Drugs

Advanced Healthcare Materials
Stefano MenegattiSamir Mitragotri

Abstract

Skin-penetrating peptides (SPPs) are attracting increasing attention as a non-invasive strategy for transdermal delivery of therapeutics. The identification of SPP sequences, however, currently performed by experimental screening of peptide libraries, is very laborious. Recent studies have shown that, to be effective enhancers, SPPs must possess affinity for both skin keratin and the drug of interest. We therefore developed a computational process for generating and screening virtual libraries of disulfide-cyclic peptides against keratin and cyclosporine A (CsA) to identify SPPs capable of enhancing transdermal CsA delivery. The selected sequences were experimentally tested and found to bind both CsA and keratin, as determined by mass spectrometry and affinity chromatography, and enhance transdermal permeation of CsA. Four heptameric sequences that emerged as leading candidates (ACSATLQHSCG, ACSLTVNWNCG, ACTSTGRNACG, and ACSASTNHNCG) were tested and yielded CsA permeation on par with previously identified SPP SPACE (TM) . An octameric peptide (ACNAHQARSTCG) yielded significantly higher delivery of CsA compared to heptameric SPPs. The safety profile of the selected sequences was also validated by incubation with skin keratinocyt...Continue Reading

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Citations

Jun 24, 2016·Pharmaceutical Patent Analyst·Hermann Am Mucke
Jul 29, 2017·Advanced Materials·Rong YangDaniel S Kohane
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Sep 4, 2021·Drug Delivery and Translational Research·Lijuan ZengWenting Song

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