Chitosan hydrogels with MK2 inhibitor peptide-loaded nanoparticles to treat atopic dermatitis

Vanessa F C Dartora; Julia Sapienza Passos; Blanca Osorio; Ruei-Chun Hung; Michael Nguyen; Aijun Wang; Alyssa Panitch

doi:10.1016/j.jconrel.2023.08.061

Chitosan hydrogels with MK2 inhibitor peptide-loaded nanoparticles to treat atopic dermatitis

J Control Release. 2023 Oct:362:591-605. doi: 10.1016/j.jconrel.2023.08.061. Epub 2023 Sep 11.

Authors

Vanessa F C Dartora¹, Julia Sapienza Passos², Blanca Osorio³, Ruei-Chun Hung¹, Michael Nguyen³, Aijun Wang⁴, Alyssa Panitch⁵

Affiliations

¹ Biomedical Engineering Graduate Group, University of California Davis, Davis, CA, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA.
² Biomedical Engineering Graduate Group, University of California Davis, Davis, CA, USA; Institute of Biomedical Sciences, Department of Pharmacology, University of Sao Paulo, Brazil.
³ Biomedical Engineering Graduate Group, University of California Davis, Davis, CA, USA.
⁴ Biomedical Engineering Graduate Group, University of California Davis, Davis, CA, USA; Department of Surgery, University of California Davis, Sacramento, CA, USA; Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, CA, USA.
⁵ Biomedical Engineering Graduate Group, University of California Davis, Davis, CA, USA; Department of Surgery, University of California Davis, Sacramento, CA, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA. Electronic address: alyssa.panitch@bme.gatech.edu.

PMID: 37660990
DOI: 10.1016/j.jconrel.2023.08.061

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that lacks ideal long-term treatment options due to a series of side effects, such as skin atrophy, related to the most common treatment prescribed to manage moderate-to-severe AD. In this study, a cell-penetrating MK2 inhibitor peptide YARA (YARAAARQARAKALNRQGLVAA) was loaded into hollow thermo-responsive pNIPAM nanoparticles (NP), which were further incorporated into chitosan hydrogels (H-NP-YARA) to promote local drug delivery, improve moisture and the anti-inflammatory activity. The NPs exhibited high loading efficiency (>50%) and the hydrogel remained porous following NP incorporation as observed by scanning electron microscopy (SEM). Both nanoparticles and hydrogels were able to improve the release of YARA and sustained release to up to 120 h. The hydrogels and NPs delivered 2 and 4-fold more YARA into viable skin layers of porcine skin in vitro at 12 h post-application than the non-encapsulated compound in intact and impaired barrier conditions. Furthermore, the YARA-loaded NPs (NP-YARA) and H-NP-YARA treatment decreased the levels of inflammatory cytokines up to 20 time-fold compared with the non-treated group of human keratinocytes under inflammatory conditions. Consistent with the results in cell culture, the loading of YARA in NP reduced the levels of IL-1β, IL-6, and TNF-α up to 3.3 times in an ex vivo skin culture model after induction of inflammation. A further decrease of up to 17 times-fold was observed with H-NP-YARA treatment compared to the drug in solution. Our data collectively suggest that chitosan hydrogel containing YARA-loaded nanoparticles is a promising new formulation for the topical treatment of AD.

Keywords: Atopic dermatitis; Chitosan; Inflammation; Nanoparticle.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chitosan* / chemistry
Dermatitis, Atopic* / drug therapy
Humans
Hydrogels / therapeutic use
Nanoparticles*
Peptides / therapeutic use
Swine

Substances

Chitosan
Hydrogels
Peptides