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Res."],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>mRNA delivered by microneedle patch (MNP) can enable painless delivery, reduced need for healthcare expertise, and improved thermostability. In this study, we investigated formulation and manufacturing approaches for developing MNPs that deliver mRNA-loaded lipid nanoparticles (LNPs) encoding luciferase as a reporter protein during MNP fabrication and storage, including mRNA-LNP concentration, formulation, pH, excipients, and backing material. MNPs were assessed for mRNA-LNP size, encapsulation efficiency, and protein expression in vitro and in vivo. MNPs fabricated with mRNA-LNPs initially prepared at a higher concentration yielded superior expression compared to mRNA-LNP concentration by centrifugation or tangential flow filtration. Acidic pH during MNP manufacturing enabled greater expression in vitro. However, no such correlation was observed in vivo. Polyvinyl alcohol (PVA) best stabilized mRNA-LNPs during the MNP manufacturing process amongst the tested polymers. Incorporating sugars in MNPs did not further improve stability. Low temperature drying (5\u00a0\u00b0C) preserved mRNA functionality better compared to drying at 25\u00a0\u00b0C and 40\u00a0\u00b0C. Though there was significant activity loss initially (87% loss in 2 days at 40\u00a0\u00b0C), mRNA expression was stabilized for extended subsequent periods even at accelerated conditions (10% additional loss after 28 days at 40\u00a0\u00b0C). Our systematic approach identified key parameters for successful formulation and manufacturing approaches to incorporate mRNA-LNPs into MNPs, which could expand access to mRNA-based medical interventions.<\/jats:p>","DOI":"10.1007\/s13346-025-01964-z","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T13:35:24Z","timestamp":1756820124000},"page":"2256-2271","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Development of a microneedle patch for delivery of mRNA-lipid nanoparticles"],"prefix":"10.1007","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9542-5444","authenticated-orcid":false,"given":"Sophia H.","family":"Sakers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0696-1721","authenticated-orcid":false,"given":"B. 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Prausnitz is an inventor of patents, a paid advisor to companies, and a founder\/shareholder of companies developing microneedle-based products. This potential conflict of interest is managed by Georgia Tech. The other authors have no competing interests to declare.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}