{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:13:45Z","timestamp":1788779625406,"version":"build-2803163510"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":91,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Sarcopenia, the age-associated loss of skeletal muscle mass and function, currently lacks effective pharmacological interventions. Pyr-Apelin-13, a potent endogenous peptide that stimulates mitochondrial biogenesis and myofiber regeneration, is limited by rapid plasma clearance and the need for frequent injections. We report the first preclinical evaluation of a transdermal Pyr-Apelin-13 microneedle (MN) patch (HeroPatch) in aged mice. The solid-state \u201cdrug-in-resin\u201d design achieved near-complete release efficiency (\n                    <jats:inline-formula>\n                      <jats:tex-math>$$\\approx$$<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    100%\n                    <jats:italic>in vitro<\/jats:italic>\n                    ; 83\u201399%\n                    <jats:italic>in vivo<\/jats:italic>\n                    ), enabling reproducible multi-milligram delivery with minimal residual loss. Daily MN dosing significantly improved muscle fiber cross-sectional area and grip strength relative to controls, with outcomes comparable to daily intraperitoneal injection. Histological analysis revealed a shift toward larger fiber sizes, consistent with enhanced myofiber remodeling, and mitochondrial DNA content increased concordantly. Weekly dosing produced smaller, non-significant trends, reflecting lower cumulative exposure. These findings demonstrate that HeroPatch enables efficient, reproducible, and non-invasive systemic delivery of Apelin-13, providing a scalable platform for peptide-based therapy of sarcopenia and related muscle-wasting disorders.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-43238-9","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T18:26:19Z","timestamp":1780943179000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microneedle patch\u2013based delivery of Pyr-Apelin-13 reverses functional and structural deficits in age-related sarcopenia"],"prefix":"10.1038","volume":"16","author":[{"given":"Chrysoula","family":"Kokotidou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Tzortzakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake","family":"Lombardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hojatollah Rezaei","family":"Nejad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"issue":"9","key":"43238_CR1","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1038\/s41591-018-0131-6","volume":"24","author":"C Vinel","year":"2018","unstructured":"Vinel, C. et al. The exerkine apelin reverses age-associated sarcopenia. Nat. Med. 24(9), 1360\u20131371. https:\/\/doi.org\/10.1038\/s41591-018-0131-6 (2018).","journal-title":"Nat. Med."},{"key":"43238_CR2","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s40266-023-01093-7","volume":"41","author":"G Bahat","year":"2024","unstructured":"Bahat, G. & Ozkok, S. The current landscape of pharmacotherapies for sarcopenia. Drugs & Aging. 41, 83\u2013112. https:\/\/doi.org\/10.1007\/s40266-023-01093-7 (2024).","journal-title":"Drugs & Aging."},{"key":"43238_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2023.155404","volume":"149","author":"Y Rolland","year":"2023","unstructured":"Rolland, Y., Dray, C., Vellas, B. & Barreto, P. S. Current and investigational medications for the treatment of sarcopenia. Metabolism 149, 155597. https:\/\/doi.org\/10.1016\/j.metabol.2023.155597 (2023).","journal-title":"Metabolism"},{"key":"43238_CR4","unstructured":"Lipocine Inc. FDA grants Fast Track designation to LPCN-1148 as a treatment for sarcopenia in patients with decompensated cirrhosis (press release). Dec 17. https:\/\/ir.lipocine.com\/2024-12-17-FDA-Grants-Fast-Track-Designation-to-Lipocine-for-LPCN-1148-as-a-Treatment-for-Sarcopenia-in-Patients-with-Decompensated-Cirrhosis (2024)."},{"key":"43238_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mser.2016.03.001","volume":"104","author":"E Larra\u00f1eta","year":"2016","unstructured":"Larra\u00f1eta, E., Lutton, R. E. M., Woolfson, A. D. & Donnelly, R. F. Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development. Mater. Sci. Eng. R Rep. 104, 1\u201332. https:\/\/doi.org\/10.1016\/j.mser.2016.03.001 (2016).","journal-title":"Mater. Sci. Eng. 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Cell Metabolism. 8(5), 437\u2013445. https:\/\/doi.org\/10.1016\/j.cmet.2008.10.003 (2008).","journal-title":"Cell Metabolism."},{"key":"43238_CR10","doi-asserted-by":"publisher","unstructured":"Enoki, Y. et al. The G protein-coupled receptor ligand apelin-13 ameliorates skeletal muscle atrophy induced by chronic kidney disease. J. Cachexia Sarcopenia Muscle 14 (1), 553\u2013564. https:\/\/doi.org\/10.1002\/jcsm.13159 (2023).","DOI":"10.1002\/jcsm.13159"},{"issue":"739","key":"43238_CR11","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abn8529","volume":"16","author":"E Le Moal","year":"2024","unstructured":"Le Moal, E. et al. Apelin stimulation of the vascular skeletal muscle stem cell niche enhances endogenous repair in dystrophic mice. Sci. Transl. 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Drug Deliv."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-43238-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-43238-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-43238-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:03:39Z","timestamp":1788779019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-43238-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,8]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["43238"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-43238-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,8]]},"assertion":[{"value":"9 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors are employees or consultants of Anodyne Nanotech, Inc., or its subsidiary Anodyne Biotech, which developed the HeroPatch\n                      \n                      microneedle platform used in this study. The authors declare no other financial or non-financial competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"27864"}}