Dissolving microneedles for long-term storage and transdermal delivery of extracellular vesicles

Van Dat Bui; Soyoung Son; Wilbin Xavier; Van Quy Nguyen; Jae Min Jung; Jungmi Lee; Sol Shin; Wooram Um; Jae Yoon An; Chan Ho Kim; Yeari Song; Yuce Li; Jae Hyung Park

doi:10.1016/j.biomaterials.2022.121644

Dissolving microneedles for long-term storage and transdermal delivery of extracellular vesicles

Biomaterials. 2022 Aug:287:121644. doi: 10.1016/j.biomaterials.2022.121644. Epub 2022 Jun 21.

Authors

Affiliations

¹ School of Chemical Engineering, College of Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea.
² School of Chemical Engineering, College of Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Republic of Korea.
³ School of Chemical Engineering, College of Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea. Electronic address: liyuce@skku.edu.
⁴ School of Chemical Engineering, College of Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Republic of Korea; Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address: jhpark1@skku.edu.

PMID: 35772350
DOI: 10.1016/j.biomaterials.2022.121644

Abstract

Extracellular vesicles (EVs) have shown great potential in disease diagnosis and treatment; however, their clinical applications remain challenging due to their unsatisfactory long-term stability and the lack of effective delivery strategies. In this study, we prepared human adipose stem cell-derived EV (hASC-EV)-loaded hyaluronic acid dissolving microneedles (EV@MN) to investigate the feasibility of EVs for their clinical applications. The biological activities of the EVs in this formulation were maintained for more than six months under mild storage conditions, especially at temperatures lower than 4 °C. Moreover, the EV@MN enabled precise and convenient intradermal delivery for sustained release of EVs in the dermis layer. Therefore, EV@MN significantly improved the biological functions of hASC-EVs on dermal fibroblasts by promoting syntheses of proteins for the extracellular matrix such as collagen and elastin, enhancing fibroblast proliferation, and regulating the phenotype of fibroblast, compared with other administration methods. This research revealed a possible and feasible formulation for the clinical application of EVs.

Keywords: Extracellular vesicle; Fibroblast; Long-term storage; Microneedle; Transdermal delivery.