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Molecules 2016, 21(10), 1279; doi:10.3390/molecules21101279

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
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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)
View Full-Text   |   Download PDF [1767 KB, uploaded 24 September 2016]   |  

Abstract

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
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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.

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