Core‐multishell nanotransporters enhance skin penetration of the cell‐penetrating peptide low molecular weight protamine

Abstract

Several peptides may enable innovative, sophisticated therapeutic approaches. Their hydrophilic nature and high molecular weight, however, often limit the applicability to topical and transdermal treatment. Aiming to enhance drug delivery to the skin, we examined the loading of two model peptides—the Cell‐Penetrating Peptides (CPPs) Low Molecular Weight Protamine (LMWP) and penetratin—to Core‐Multishell (CMS) nanotransporters which are well tolerated and known to enhance skin penetration most efficiently. Furthermore, we followed skin penetration of dye‐tagged LMWP in the presence of CMS nanotransporters taking enzymatic peptide cleavage into account. As expected, Isothermal Titration Calorimetry indicated that the large peptides do not interact with CMS nanotransporters. Additionally, size exclusion chromatography and Dynamic Light Scattering confirmed no loading of CPPs to CMS nanoparticles. Due to less LMWP aggregation, concomitant topical application of LMWP and CMS nanotransporters did not enhance the penetration of intact LWMP but enhanced the penetration of peptide fragments in viable layers of human skin ex vivo. Conclusively, our results indicate that CMS nanotransporters impair the skin barrier function leading to increased skin penetration of less voluminous peptides, which may be of future clinical relevance—in particular with those failing to be CPPs. Copyright © 2014 John Wiley & Sons, Ltd.