Next Article in Journal
Nanostructured Samarium Doped Fluorapatites and Their Catalytic Activity towards Synthesis of 1,2,4-Triazoles
Next Article in Special Issue
Synthesis of Polymer-Lipid Nanoparticles by Microfluidic Focusing for siRNA Delivery
Previous Article in Journal
Anti-Inflammatory Activity of Citrus bergamia Derivatives: Where Do We Stand?
Previous Article in Special Issue
Delivery of RNAi Therapeutics to the Airways—From Bench to Bedside
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Molecules 2016, 21(10), 1279;

Development of an Innovative Intradermal siRNA Delivery System Using a Combination of a Functional Stearylated Cytoplasm-Responsive Peptide and a Tight Junction-Opening Peptide

Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Author to whom correspondence should be addressed.
Academic Editors: Wong Wai-Shiu and Derek J. McPhee
Received: 29 July 2016 / Revised: 30 August 2016 / Accepted: 17 September 2016 / Published: 24 September 2016
(This article belongs to the Special Issue Nucleic Acid-based Drug)
Full-Text   |   PDF [1767 KB, uploaded 24 September 2016]   |  


As a new category of therapeutics for skin diseases including atopic dermatitis (AD), nucleic acids are gaining importance in the clinical setting. Intradermal administration is noninvasive and improves patients′ quality of life. However, intradermal small interfering RNA (siRNA) delivery is difficult because of two barriers encountered in the skin: intercellular lipids in the stratum corneum and tight junctions in the stratum granulosum. Tight junctions are the major barrier in AD; therefore, we focused on functional peptides to devise an intradermal siRNA delivery system for topical skin application. In this study, we examined intradermal siRNA permeability in the tape-stripped (20 times) back skin of mice or AD-like skin of auricles treated with 6-carboxyfluorescein-aminohexyl phosphoramidite (FAM)-labeled siRNA, the tight junction modulator AT1002, and the functional cytoplasm-responsive stearylated peptide STR-CH2R4H2C by using confocal laser microscopy. We found that strong fluorescence was observed deep and wide in the epidermis and dermis of back skin and AD-like ears after siRNA with STR-CH2R4H2C and AT1002 treatment. After 10 h from administration, brightness of FAM-siRNA was significantly higher for STR-CH2R4H2C + AT1002, compared to other groups. In addition, we confirmed the nontoxicity of STR-CH2R4H2C as a siRNA carrier using PAM212 cells. Thus, our results demonstrate the applicability of the combination of STR-CH2R4H2C and AT1002 for effective intradermal siRNA delivery. View Full-Text
Keywords: drug delivery; transdermal; siRNA; peptide; atopic dermatitis drug delivery; transdermal; siRNA; peptide; atopic dermatitis

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Ibaraki, H.; Kanazawa, T.; Takashima, Y.; Okada, H.; Seta, Y. Development of an Innovative Intradermal siRNA Delivery System Using a Combination of a Functional Stearylated Cytoplasm-Responsive Peptide and a Tight Junction-Opening Peptide. Molecules 2016, 21, 1279.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top