Chondroitin sulfate-based microneedles for transdermal delivery of stem cell-derived extracellular vesicles to treat rheumatoid arthritis

For the non-invasive treatment of rheumatoid arthritis (RA), a chondroitin sulfate C (CSC)-based dissolving microneedles (cMN) was prepared to deliver human adipose stem cell-derived extracellular vesicles (hASC-EV) into inflamed joints. Owing to their anti-inflammatory function, the hASC-EV-bearing...

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Bibliographic Details
Published in:Journal of controlled release 2024-11, Vol.375, p.105-115
Main Authors: Bui, Van Dat, Jeon, Jueun, Duong, Van Hieu, Shin, Sol, Lee, Jungmi, Ghahari, Farrokhroo, Kim, Chan Ho, Jo, Yu Jin, Jung, Won-Kyo, Um, Wooram, Park, Jae Hyung
Format: Article
Language:English
Subjects:
Chondroitin sulfate
Dissolving microneedles
Extracellular vesicles
Fibroblast-like Synoviocytes
Macrophages
Rheumatoid arthritis
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Summary:For the non-invasive treatment of rheumatoid arthritis (RA), a chondroitin sulfate C (CSC)-based dissolving microneedles (cMN) was prepared to deliver human adipose stem cell-derived extracellular vesicles (hASC-EV) into inflamed joints. Owing to their anti-inflammatory function, the hASC-EV-bearing cMN (EV@cMN) significantly suppressed activated fibroblast-like synoviocytes (aFLS) and M1 macrophages (M1), which are responsible for the progression of RA. In addition, EV@cMN facilitated the chondrogenic differentiation of bone marrow-derived stem cells. In mice with collagen-induced arthritis, EV@cMN efficiently delivered both hASC-EV and CSC to inflamed joints. Interestingly, pro-inflammatory cytokines in the inflamed joints were remarkably downregulated by the synergistic effect of CSC and hASC-EV. Consequently, as judged from the overall clinical score and joint swelling, EV@cMN showed an outstanding therapeutic effect, even comparable to the wild-type mice, without significant adverse effects. Overall, EV@cMN might have therapeutic potential for RA by efficiently delivering CSC and hASC-EV into the inflamed joints in a non-invasive manner. [Display omitted] •Macrophages and synoviocytes contribute significantly to the progression of rheumatoid arthritis.•Stem cell-derived extracellular vesicle (hASC-EV) inhibits M1 polarization of macrophages.•We discovered that chondroitin sulfate (CSC) reduces the invasiveness of synoviocytes.•Co-delivery of hASC-EV and CSC via microneedle effectively inhibits the progression of RA.
ISSN:0168-3659
1873-4995
1873-4995
DOI:10.1016/j.jconrel.2024.08.050