Surface-Modified Diatom Nanoparticles for Targeted Naproxen Delivery and Toxicity Assessment Using Zebrafish Embryo Model

Surface-Modified Diatom Nanoparticles for Targeted Naproxen Delivery and Toxicity Assessment Using Zebrafish Embryo Model | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Surface-Modified Diatom Nanoparticles for Targeted Naproxen Delivery and Toxicity Assessment Using Zebrafish Embryo Model Selvakumar Sakthivel, Tanuja Abdulla This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8890533/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract This study focuses on enhancing the targeting efficiency of surface-modified diatom nanoparticles (DNPs) as carriers for naproxen. Diatom nanoparticles fabricated from diatomaceous earth using hot alcoholic acid treatments followed by calcination and surface functionalization with 3-aminopropyltriethoxysilane (APTE). DNPs and APTES-DNPs were characterized by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and thermogravimetric differential thermal analysis (TGDTA). APTES-DNPs exhibited small, polyshaped particles with a high naproxen loading content (23.47 ± 0.41%) and encapsulation efficiency (84.84 ± 1.2%). FTIR and XRD confirmed the presence of amine groups and crystallinity, while EDX and TGDTA analysis indicated the presence of essential elements and endothermic properties at 381°C for DNPs and 293°C for APTES-DNPs. In-vitro drug release studies revealed sustained naproxen release for 87.6% (± 5.6) over 300 minutes at pH 7.4, with release kinetics best fitting the First order model (R²=0.9464) and Hixson-Crowell model (R²=0.9550). Zebrafish embryo toxicity assays assessed hatching rate, mortality, and malformation at 12, 24, 48, 72, and 96 post-fertilization hours (pfh) by DNPs and APTES-DNPs. LC 50 values calculated by probit analysis along with 95% confidence limits, were 125.24 mg/L for DNPs and 453.00 mg/L for APTES-DNPs. APTES-DNPs caused a more reduction in hatching rates and mortality percentage compared to unmodified DNPs, reflecting higher bioavailability and cellular uptake. Overall, the findings suggest that surface-functionalized diatom nanoparticles are promising, pH-sensitive, cost-effective, and eco-friendly drug delivery systems. They offer potential for targeted delivery of Naproxen and may be further explored for acute gastroenteritis. Diatom Nanoparticles APTES Surface functionalization Naproxen Drug Release Kinetics Zebrafish embryo toxicity Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 04 Mar, 2026 Editor assigned by journal 04 Mar, 2026 Submission checks completed at journal 03 Mar, 2026 First submitted to journal 16 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8890533","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":600476712,"identity":"04934b78-cd47-4ade-84f6-f923a18d97a8","order_by":0,"name":"Selvakumar Sakthivel","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2UlEQVRIiWNgGAWjYFAC5gYIzQ6iDSyI0cII0cLDcwCkRYIULRIJIIoILfLtjW0SPxju2NtLPr+64UeBBAN/e3cCXi0GZw62SfYwPGPmkc4pu9kDdJjEmbMb8GuRSGw24GE4zAbUknaDB6jFQCIXvxb5+Q+bDf8wHObhkTyTdvMPMVoYbjA2PgbaIsEjwX7sNlG2GJxJbHwsY3DYgOdMDtttGQOgVkJ+kW8/fODgm4rD9uztx5/dfPPHRo6/vZeAwyB2gQgeCEmEcjhgf0CK6lEwCkbBKBhBAADuL0LfcJL2NAAAAABJRU5ErkJggg==","orcid":"","institution":"G.Venkataswamy Naidu College","correspondingAuthor":true,"prefix":"","firstName":"Selvakumar","middleName":"","lastName":"Sakthivel","suffix":""},{"id":600476713,"identity":"1fbec4cc-4ea9-40e5-93fc-efcf130272c7","order_by":1,"name":"Tanuja Abdulla","email":"","orcid":"","institution":"ICAR-Central Inland Fisheries Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Tanuja","middleName":"","lastName":"Abdulla","suffix":""}],"badges":[],"createdAt":"2026-02-16 07:08:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8890533/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8890533/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104402864,"identity":"3a29441f-cd87-4891-a9c7-1400d620928b","added_by":"auto","created_at":"2026-03-11 12:16:44","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1410974,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8890533/v1_covered_c6f532c8-2344-46f0-be33-7ea20cdce94f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Surface-Modified Diatom Nanoparticles for Targeted Naproxen Delivery and Toxicity Assessment Using Zebrafish Embryo Model","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bionanoscience","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnsc","sideBox":"Learn more about [BioNanoScience](http://link.springer.com/journal/12668)","snPcode":"12668","submissionUrl":"https://submission.nature.com/new-submission/12668/3","title":"BioNanoScience","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Diatom Nanoparticles, APTES Surface functionalization, Naproxen, Drug Release Kinetics, Zebrafish embryo toxicity","lastPublishedDoi":"10.21203/rs.3.rs-8890533/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8890533/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study focuses on enhancing the targeting efficiency of surface-modified diatom nanoparticles (DNPs) as carriers for naproxen. Diatom nanoparticles fabricated from diatomaceous earth using hot alcoholic acid treatments followed by calcination and surface functionalization with 3-aminopropyltriethoxysilane (APTE). DNPs and APTES-DNPs were characterized by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and thermogravimetric differential thermal analysis (TGDTA). APTES-DNPs exhibited small, polyshaped particles with a high naproxen loading content (23.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41%) and encapsulation efficiency (84.84\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2%). FTIR and XRD confirmed the presence of amine groups and crystallinity, while EDX and TGDTA analysis indicated the presence of essential elements and endothermic properties at 381\u0026deg;C for DNPs and 293\u0026deg;C for APTES-DNPs. \u003cem\u003eIn-vitro\u003c/em\u003e drug release studies revealed sustained naproxen release for 87.6% (\u0026plusmn;\u0026thinsp;5.6) over 300 minutes at pH 7.4, with release kinetics best fitting the First order model (R\u0026sup2;=0.9464) and Hixson-Crowell model (R\u0026sup2;=0.9550). Zebrafish embryo toxicity assays assessed hatching rate, mortality, and malformation at 12, 24, 48, 72, and 96 post-fertilization hours (pfh) by DNPs and APTES-DNPs. LC\u003csub\u003e50\u003c/sub\u003e values calculated by probit analysis along with 95% confidence limits, were 125.24 mg/L for DNPs and 453.00 mg/L for APTES-DNPs. APTES-DNPs caused a more reduction in hatching rates and mortality percentage compared to unmodified DNPs, reflecting higher bioavailability and cellular uptake. Overall, the findings suggest that surface-functionalized diatom nanoparticles are promising, pH-sensitive, cost-effective, and eco-friendly drug delivery systems. They offer potential for targeted delivery of Naproxen and may be further explored for acute gastroenteritis.\u003c/p\u003e","manuscriptTitle":"Surface-Modified Diatom Nanoparticles for Targeted Naproxen Delivery and Toxicity Assessment Using Zebrafish Embryo Model","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-06 06:19:22","doi":"10.21203/rs.3.rs-8890533/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-03-04T08:40:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-04T08:12:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-03T23:54:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"BioNanoScience","date":"2026-02-16T06:52:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bionanoscience","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnsc","sideBox":"Learn more about [BioNanoScience](http://link.springer.com/journal/12668)","snPcode":"12668","submissionUrl":"https://submission.nature.com/new-submission/12668/3","title":"BioNanoScience","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"65aca624-f458-420d-9ff4-1baf53a91962","owner":[],"postedDate":"March 6th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-06T06:19:22+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-06 06:19:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8890533","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8890533","identity":"rs-8890533","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}