pH-responsive hydrogel facilitates skin penetration of extracellular vesicle-like nanovesicles for enhanced atopic dermatitis therapy
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disorder, and the long-term use of topical corticosteroids is often limited by adverse effects and poor tolerability. Herein, we developed CAAM-G, a corticosteroid-free hydrogel platform composed of carboxymethyl cellulose, acrylamide and acrylic acid, and loaded with Gentiana macrophylla Pall.-derived extracellular vesicle-like nanovesicles (GELNs) and L-menthol. The hydrogel exhibited favorable mechanical properties, tissue adhesion and swelling capacity. Under mildly to moderately alkaline conditions relevant to lesional AD skin, it exhibited pH-dependent release of GELNs and menthol. The released menthol enhanced the cutaneous distribution of PKH26-labeled GELN-associated fluorescence in a porcine skin Franz diffusion model. In vitro, GELN-containing formulations efficiently scavenged reactive oxygen species, suppressed pro-inflammatory cytokine secretion and promoted macrophage polarization toward an M2-like phenotype. In the 2,4-dinitro-1-fluorobenzene-induced AD-like mouse model, the high-dose formulation, CAAM-GH, significantly alleviated ear swelling, epidermal thickening, mast cell infiltration and other AD-like manifestations. For several evaluated endpoints, CAAM-GH produced greater improvement than the dexamethasone reference group. No evident treatment-associated systemic toxicity was detected under the experimental conditions. Integrated transcriptomic and Western blot analyses indicated suppression of nuclear factor-kappa B (NF-κB)-associated pro-inflammatory signaling. These findings support CAAM-G as a promising corticosteroid-free topical platform for the treatment of AD, although further pharmacological and toxicological evaluation is required before clinical translation.
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BibTeX
@article{li2026phresponsive,
title = {{pH-responsive hydrogel facilitates skin penetration of extracellular vesicle-like nanovesicles for enhanced atopic dermatitis therapy}},
author = {Kaizheng Li and Mengnan Dai and Chao Xu and Zengjie Fan},
journal = {Regenerative Biomaterials},
year = {2026},
month = sep,
doi = {10.1093/rb/rbag196},
url = {https://doi.org/10.1093/rb/rbag196},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - pH-responsive hydrogel facilitates skin penetration of extracellular vesicle-like nanovesicles for enhanced atopic dermatitis therapy
AU - Kaizheng Li
AU - Mengnan Dai
AU - Chao Xu
AU - Zengjie Fan
PY - 2026
DA - 2026/09/03
JO - Regenerative Biomaterials
DO - 10.1093/rb/rbag196
UR - https://doi.org/10.1093/rb/rbag196
AB - Atopic dermatitis (AD) is a chronic inflammatory skin disorder, and the long-term use of topical corticosteroids is often limited by adverse effects and poor tolerability. Herein, we developed CAAM-G, a corticosteroid-free hydrogel platform composed of carboxymethyl cellulose, acrylamide and acrylic acid, and loaded with Gentiana macrophylla Pall.-derived extracellular vesicle-like nanovesicles (GELNs) and L-menthol. The hydrogel exhibited favorable mechanical properties, tissue adhesion and swelling capacity. Under mildly to moderately alkaline conditions relevant to lesional AD skin, it exhibited pH-dependent release of GELNs and menthol. The released menthol enhanced the cutaneous distribution of PKH26-labeled GELN-associated fluorescence in a porcine skin Franz diffusion model. In vitro, GELN-containing formulations efficiently scavenged reactive oxygen species, suppressed pro-inflammatory cytokine secretion and promoted macrophage polarization toward an M2-like phenotype. In the 2,4-dinitro-1-fluorobenzene-induced AD-like mouse model, the high-dose formulation, CAAM-GH, significantly alleviated ear swelling, epidermal thickening, mast cell infiltration and other AD-like manifestations. For several evaluated endpoints, CAAM-GH produced greater improvement than the dexamethasone reference group. No evident treatment-associated systemic toxicity was detected under the experimental conditions. Integrated transcriptomic and Western blot analyses indicated suppression of nuclear factor-kappa B (NF-κB)-associated pro-inflammatory signaling. These findings support CAAM-G as a promising corticosteroid-free topical platform for the treatment of AD, although further pharmacological and toxicological evaluation is required before clinical translation.
SN - 2056-3418
SN - 2056-3426
ER -