Transdermal anti-nuclear kappaB siRNA therapy for atopic dermatitis using a combination of two kinds of functional oligopeptide.
Int J Pharm
; 542(1-2): 213-220, 2018 May 05.
Article
in En
| MEDLINE
| ID: mdl-29551748
ABSTRACT
Nucleic acid-based targeting of nuclear factor kappaB (NF-κB) is gaining attention as a treatment option for skin diseases like atopic dermatitis (AD). Transdermal administration improves patient quality of life because of non-invasive; however, siRNA delivery into the skin can be challenging owing to the barrier of tight junctions in the granular layer. Therefore, we aimed to develop a delivery system of siRNA for topical skin application using functional peptides. We previously reported that combined treatment with a cytoplasm-responsive stearylated-arginine-rich peptide (STR-CH2R4H2C) and a tight junction opening peptide (AT1002) showed high siRNA permeability in the skin of AD-induced and normal mice. Here, we used murine macrophage RAW264.7 cells to examine siRNA permeation and the therapeutic effect of anti-NF-κB (RelA) siRNA (siRelA) complexed with STR-CH2R4H2C and AT1002 for AD-induced mice. We showed that significantly higher siRNA cellular uptake occurs after this treatment as well as decreased TNF-α and IL-6 expression. Additionally, we showed that effective siRNA transdermal delivery occurs with the suppression of the tight junction protein ZO-1. Moreover, topical skin application of siRelA with STR-CH2R4H2C and AT1002 improved AD-like symptoms in model mice. Thus, the combined treatment of STR-CH2R4H2C and AT1002 could serve as an effective transdermal siRNA therapeutic system for AD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligopeptides
/
NF-kappa B
/
RNA, Small Interfering
/
Dermatitis, Atopic
Type of study:
Prognostic_studies
Aspects:
Patient_preference
Limits:
Animals
Language:
En
Journal:
Int J Pharm
Year:
2018
Document type:
Article
Affiliation country: