Innovative Microneedle Patches for Psoriasis Treatment: A Dual Approach With Methotrexate-Zinc and Difelikefalin for Enhanced Therapeutic Outcomes.

Xu X, Long C, Zhou Y, Fei L, Zhou Y, Qi M

Small (Weinheim an der Bergstrasse, Germany)30 May 2026Cited by 1 (Europe PMC)

PMID42216778PMCIDPMC13306916DOI10.1002/smll.73958PepBankPUB-42216778

Summary

Psoriasis is a chronic inflammatory skin disease often accompanied by pruritus and a high risk of secondary infection. To address the limitations of current therapies, we developed a dual-layer microneedle (MN) system that integrates methotrexate-zinc (MTX-Zn) for sustained anti-inflammatory and antibacterial effects with difelikefalin (DFK) for rapid antipruritic action. MTX-Zn was successfully synthesized through coordination chemistry and exhibited enhanced stability, preserved antiproliferative activity, and strong antibacterial effects. The GelMA/PVA-based microneedles showed excellent mechanical strength, efficient skin penetration, and distinct spatial drug compartmentalization. In an IMQ-induced psoriasis model, MTX-Zn/DFK MNs markedly improved clinical symptoms, reduced epidermal hyperplasia, restored immune-cell homeostasis, and decreased Th17/Th1-mediated inflammation. DFK-loaded MNs rapidly alleviated pruritus, reduced epidermal nerve-fiber density, and inhibited Schwann cell migration. Transcriptomic analysis further revealed that DFK suppressed Schwann cell EMT pathways. Together, this dual-functional microneedle platform provides a synergistic therapeutic strategy that combines rapid itch relief with long-term anti-psoriatic and antibacterial effects, representing a promising approach for improving psoriasis management.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

01AnimalOther designMechanism
In a psoriasis model, difelikefalin-loaded microneedles rapidly alleviated pruritus, reduced epidermal nerve-fiber density, and inhibited Schwann cell migration.
In plain wordsIn a psoriasis model, difelikefalin-loaded microneedles rapidly reduced itching, skin nerve-fiber density, and Schwann cell migration.
Peptide
Difelikefalin
Outcome
DecreasePruritus, nerve-fiber density and Schwann cell migration
Study
n: not reported in source
Outcome group
Skin and hair · Skin and wound
Studied dose
Dose not stated
Source sentences
Summary
DFK-loaded MNs rapidly alleviated pruritus, reduced epidermal nerve-fiber density, and inhibited Schwann cell migration.
Show in the study text Report a problemFND-4221677801
02LabOther designMechanism
In transcriptomic analysis of the difelikefalin-loaded microneedle system, difelikefalin suppressed Schwann cell EMT pathways.
In plain wordsIn transcriptomic analysis of the difelikefalin-loaded microneedle system, difelikefalin suppressed Schwann cell EMT pathways.
Peptide
Difelikefalin
Outcome
DecreaseSchwann cell EMT pathways
Study
n: not reported in source
Outcome group
Skin and hair · Skin and wound
Studied dose
Dose not stated
Source sentences
Summary
Transcriptomic analysis further revealed that DFK suppressed Schwann cell EMT pathways.
Show in the study text Report a problemFND-4221677802

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Version history

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Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:35 UTC
First added · source update from Europe PMC

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