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Res."],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This study introduces vacuum compression molding (VCM) as a novel, solvent-free method for fabricating palonosetron hydrochloride (PAL HCl)-loaded polyvinyl alcohol (PVA) microneedles (MNs), addressing limitations of conventional micromolding such as extended drying times, batch variability, and solvent residues. PAL HCl-a hydrophilic 5-HT3 receptor antagonist (MW: 332.85\u00a0g\/mol) with a low therapeutic dose-was selected for its clinical relevance in managing chemotherapy-induced nausea and vomiting (CINV). The microneedle platform offers advantages over PAL HCl\u2019s existing oral and injectable dosage forms, including pain-free application and improved patient compliance. The aim of this research is to develop and evaluate a scalable VCM-based fabrication approach for PAL HCl-loaded PVA microneedles, with the goal of achieving sustained, three-day in vitro transdermal drug delivery for improved CINV management. Ten PVA grades (varying in molecular weight and viscosity) were screened to optimize microneedle fabrication. Three formulations-M1 (particle-engineered PVA 4\u201388), M4 (PVA 5\u201388), and M5 (PVA 8\u201388)-demonstrated optimal mechanical strength, uniform geometry (SEM imaging), and reliable skin penetration (~\u2009200\u00a0\u03bcm depth in dermatomed human skin). Physicochemical characterization (FTIR, DSC) confirmed the amorphous state of PAL HCl within the PVA matrix and the absence of chemical interactions. In vitro release testing revealed biphasic profiles: an initial burst release for 8\u00a0h followed by sustained release over 72\u00a0h. Cumulative release inversely correlated with PVA molecular weight and viscosity, with M1 achieving 100% release, compared to M4 (74%) and M5 (67%). Permeation studies demonstrated M1\u2019s superior performance (257.56\u2009\u00b1\u200929.73\u00a0\u00b5g\/sq cm), exceeding passive diffusion by 8.8-fold and significantly outperforming M4 (64.99\u2009\u00b1\u200930.23\u00a0\u00b5g\/ sq cm) and M5 (39.03\u2009\u00b1\u200920.20\u00a0\u00b5g\/sq cm). These results validate VCM as a scalable, tunable platform for fabricating PAL HCl-drug-loaded microneedles, offering sustained transdermal delivery with clinical potential for CINV management.<\/jats:p>","DOI":"10.1007\/s13346-025-01980-z","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T16:44:50Z","timestamp":1758645890000},"page":"1788-1807","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Vacuum compression-molded polyvinyl alcohol microneedles for sustained three-day transdermal delivery of palonosetron hydrochloride"],"prefix":"10.1007","volume":"16","author":[{"given":"Meheli","family":"Ghosh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharvari M.","family":"Kshirsagar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kipping","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4005-5359","authenticated-orcid":false,"given":"Ajay K.","family":"Banga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"1980_CR1","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1038\/nbt.1504","volume":"26","author":"MR Prausnitz","year":"2008","unstructured":"Prausnitz MR, Langer R. 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