Neurog1-Derived Peptides RMNE1 and DualPep-Shine Penetrate the Skin and Inhibit Melanin Synthesis by Regulating MITF Transcription

Abstract

Anti-pigmentation peptides have been developed as alternative skin-lightening agents to replace conventional chemicals that have adverse effects on the skin. However, the maximum size of these peptides is often limited by their low skin and cell penetration. To address this issue, we used our intra-dermal delivery technology (IDDT) platform to identify peptides with hypo-pigmenting and high cell-penetrating activity. Using our cell-penetrating peptides (CPPs) from the IDDT platform, we identified RMNE1 and its derivative RMNE3, “DualPep-Shine”, which showed levels of α-Melanocyte stimulating hormone (α-MSH)-induced melanin inhibition comparable to the conventional tyrosinase inhibitor, Kojic acid. In addition, DualPep-Shine was delivered into the nucleus and regulated the gene expression levels of melanogenic enzymes by inhibiting the promoter activity of microphthalmia-associated transcription factor-M (MITF-M). Using a 3D human skin model, we found that DualPep-Shine penetrated the lower region of the epidermis and reduced the melanin content in a dose-dependent manner. Furthermore, DualPep-Shine showed high safety with little immunogenicity, indicating its potential as a novel cosmeceutical ingredient and anti-pigmentation therapeutic agent.

Transdermal Properties of Cell-Penetrating Peptides: Applications and Skin Penetration Mechanisms

“…The 3D Episkin model has been used in a study to evaluate the translocation process of nanoparticles across the skin and to investigate the mechanism underlying the diverse epidermal penetration behaviors of gold nanoparticles with different surface charges . The 3D human skin Neoderm-ME model was used to assess the whitening effects and inhibition of melanin synthesis of antipigmentation peptides, Neurog1-derived peptides, as a novel cosmeceutical ingredient and antipigmentation therapeutic agent …”

“…99 The 3D human skin Neoderm-ME model was used to assess the whitening effects and inhibition of melanin synthesis of antipigmentation peptides, Neurog1-derived peptides, as a novel cosmeceutical ingredient and antipigmentation therapeutic agent. 100 Despite the high potential as an alternative replacement of animal models, there are some limitations to using artificial skin models. Although several primary cell lines, such as keratinocytes, fibroblasts, and epithelial cells, are used in skin reconstruction procedures, current skin models are limited in that they include some ingredients and cells that are originally from human skin, which differs from the in vivo skin environment in the tissue development process.…”