. 2025 May 15.

doi: 10.1007/s13346-025-01876-y. Online ahead of print.

Synergy of dissolving microneedles and ultrasound to enhance transdermal delivery for rheumatoid arthritis

Wangrui Peng^#^{1

2

3}, MeeiChyn Goh^#^{1

2}, Jie Lan^{1

2

3}, Meng Du^{1

2}, Zhiyi Chen^{4

5

6}

Affiliations

¹ Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, College of Hunan Province, the Affiliated Changsha Central Hospital, University of South China, Changsha, China.
² Institute of Medical Imaging, Hengyang Medical School, University of South China, Hengyang, China.
³ The Seventh Affiliated Hospital, Hengyang Medical School, University of South China (Hunan Provincial Veterans Administration Hospital), Changsha, Hunan, China.
⁴ Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, College of Hunan Province, the Affiliated Changsha Central Hospital, University of South China, Changsha, China. zhiyi_chen@usc.edu.cn.
⁵ Institute of Medical Imaging, Hengyang Medical School, University of South China, Hengyang, China. zhiyi_chen@usc.edu.cn.
⁶ Department of Medical Imaging, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, 161 ShaoShan South Road, Changsha, 410004, Hunan, China. zhiyi_chen@usc.edu.cn.

^# Contributed equally.

PMID: 40372697
DOI: 10.1007/s13346-025-01876-y

Synergy of dissolving microneedles and ultrasound to enhance transdermal delivery for rheumatoid arthritis

Wangrui Peng et al. Drug Deliv Transl Res. 2025.

. 2025 May 15.

doi: 10.1007/s13346-025-01876-y. Online ahead of print.

Authors

Wangrui Peng^#^{1

2

3}, MeeiChyn Goh^#^{1

2}, Jie Lan^{1

2

3}, Meng Du^{1

2}, Zhiyi Chen^{4

5

6}

Affiliations

¹ Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, College of Hunan Province, the Affiliated Changsha Central Hospital, University of South China, Changsha, China.
² Institute of Medical Imaging, Hengyang Medical School, University of South China, Hengyang, China.
³ The Seventh Affiliated Hospital, Hengyang Medical School, University of South China (Hunan Provincial Veterans Administration Hospital), Changsha, Hunan, China.
⁴ Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, College of Hunan Province, the Affiliated Changsha Central Hospital, University of South China, Changsha, China. zhiyi_chen@usc.edu.cn.
⁵ Institute of Medical Imaging, Hengyang Medical School, University of South China, Hengyang, China. zhiyi_chen@usc.edu.cn.
⁶ Department of Medical Imaging, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, 161 ShaoShan South Road, Changsha, 410004, Hunan, China. zhiyi_chen@usc.edu.cn.

^# Contributed equally.

PMID: 40372697
DOI: 10.1007/s13346-025-01876-y

Abstract

Dissolving microneedles (DMNs) are an emerging transdermal drug delivery system that has gained increasing attention as an alternative to traditional oral and injectable methods for treating rheumatoid arthritis (RA). However, these DMNs encounter challenges related to insufficient drug diffusion through passive mechanisms. To address this issue, we developed biocompatible DMNs fabricated from hyaluronic acid (HA) loaded with ultrasound-responsive nanoparticles, aiming at enhancing drug permeation and diffusion through ultrasound (US) assistance. Methotrexate (MTX), a first-line treatment for RA, was encapsulated in poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles containing perfluoro-n-pentane (PFP), referred to as MTX-PFP-NPs. These nanoparticles were then incorporated into DMNs, designated as MTX-PFP-NPs@DMNs. Under the cavitation effect of ultrasound, PFP undergoes a phase transition that facilitates drug release and diffusion. The synergistic effect of the DMNs system and US were demonstrated in both an ex-vivo rat skin model and a collagen-induced arthritis (CIA) mouse model. The MTX-PFP-NPs@DMNs exhibited sufficient mechanical strength to penetrate the stratum corneum and dissolve completely within 20 min, enabling effective drug delivery. The synergistic effect of the DMNs system and US was evidenced by enhanced FITC penetration and diffusion in the ex-vivo rat skin model. Additionally, in vivo studied showed improved therapeutic efficacy in reducing joint swelling, bone erosion, cartilage damage, and pro-inflammatory cytokines level compared to only MTX-PFP-NPs@DMNs. This research underscores the promising integration of DMNs technology and US, offering a high-compliance approach to transdermal drug delivery that could significantly improve treatment outcomes for chronic conditions like RA.

Keywords: Dissolving microneedles; Drug diffusion; Rheumatoid arthritis; Transdermal drug delivery; Ultrasound-responsive.

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Conflict of interest statement

Declarations. Ethics approval: All animal experimental procedures were approved by the Ethics Committee on Laboratory Animals of the University of South China. Consent for publication: Not applicable. Competing interests: All authors have agreed with publication of the manuscript.

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Synergy of dissolving microneedles and ultrasound to enhance transdermal delivery for rheumatoid arthritis

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Synergy of dissolving microneedles and ultrasound to enhance transdermal delivery for rheumatoid arthritis

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