Abstract | BACKGROUND:
Atopic dermatitis (AD) and psoriasis are the 2 most common chronic inflammatory skin diseases. There is an unmet medical need to overcome limitations for transcutaneous drug development posed by the skin barrier. OBJECTIVE: We aimed to identify a novel transdermal delivery peptide and to develop a transcutaneously applicable immunomodulatory protein for treating AD and psoriasis. METHODS: RESULTS: AP-conjugated reporter proteins exhibited significant intracellular transduction efficacy in keratinocytes, fibroblasts, and immune cells. In addition, transcutaneous administration of AP-dTomato resulted in significant localization into the dermis and epidermis in both mouse and human skin. AP-rPTP inhibited phosphorylated signal transducer and activator of transcription (STAT) 1, STAT3, and STAT6 in splenocytes and also regulated T-cell activation and proliferation. Transcutaneous administration of AP-rPTP through the paper-patch technique significantly ameliorated skin tissue thickening, inflammation, and cytokine expression in both AD-like and psoriasis-like dermatitis models. CONCLUSION: We identified a 9-amino-acid novel transdermal delivery peptide, AP, and demonstrated its feasibility for transcutaneous biologic drug development. Moreover, AP-rPTP is a novel immunomodulatory drug candidate for human dermatitis.
|
Authors | Won-Ju Kim, Ja-Hyun Koo, Hyun-Jung Cho, Jae-Ung Lee, Ji Yun Kim, Hong-Gyun Lee, Sohee Lee, Jong Hoon Kim, Mi Seon Oh, Minah Suh, Eui-Cheol Shin, Joo Yeon Ko, Myung Hyun Sohn, Je-Min Choi |
Journal | The Journal of allergy and clinical immunology
(J Allergy Clin Immunol)
Vol. 141
Issue 1
Pg. 137-151
(01 2018)
ISSN: 1097-6825 [Electronic] United States |
PMID | 28456618
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- ASTN2 protein, human
- Glycoproteins
- Nerve Tissue Proteins
- Peptides
- Recombinant Fusion Proteins
- STAT Transcription Factors
- Protein Tyrosine Phosphatase, Non-Receptor Type 2
|
Topics |
- Animals
- Dermatitis, Atopic
(drug therapy, immunology, pathology)
- Dermis
(immunology, pathology)
- Glycoproteins
(genetics, pharmacology)
- Humans
- Mice
- Mice, Inbred BALB C
- Nerve Tissue Proteins
(genetics, pharmacology)
- Peptides
(genetics, pharmacology)
- Protein Tyrosine Phosphatase, Non-Receptor Type 2
(genetics, pharmacology)
- Psoriasis
(drug therapy, immunology, pathology)
- Recombinant Fusion Proteins
(genetics, pharmacology)
- STAT Transcription Factors
(immunology)
|