Mesoporous Nanoparticle-Mediated Ratio-metric & Controlled Release of D-Cycloserine and Levofloxacin: Comparing Chloroacetyl Chloride and Succinyl Chloride Conjugates with Physical Mixture for MDR Tuberculosis Treatment

Mesoporous Nanoparticle-Mediated Ratio-metric & Controlled Release of D-Cycloserine and Levofloxacin: Comparing Chloroacetyl Chloride and Succinyl Chloride Conjugates with Physical Mixture for MDR Tuberculosis Treatment | 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 Mesoporous Nanoparticle-Mediated Ratio-metric & Controlled Release of D-Cycloserine and Levofloxacin: Comparing Chloroacetyl Chloride and Succinyl Chloride Conjugates with Physical Mixture for MDR Tuberculosis Treatment Nagashubha B, Dr. Padmanabha Reddy Y, Azger Dusthackeer VN, Dr. Lalit kumar This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6422681/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: The treatment of multi-drug-resistant tuberculosis (MDR-TB) is complicated by resistance to multiple anti-tubercular drugs. This study explores a mesoporous nanoparticle-based approach for the ratiometric and controlled delivery of D-Cycloserine and Levofloxacin to combat MDR-TB. Objective: To synthesize, characterize, and compare the efficacy of mesoporous nanoparticles loaded with D-Cycloserine and Levofloxacin conjugates, using Chloroacetyl Chloride (CAC) and Succinyl Chloride (SCL) as cross-linkers, against a physical mixture for MDR-TB treatment. Methods: Two dual-drug conjugates were synthesized: D-Cycloserine-Chloroacetyl Chloride-Levofloxacin (DCL) and D-Cycloserine-Succinyl Chloride-Levofloxacin (DSL). The conjugates' stability was assessed via hydrolysability testing. Both conjugates, along with a physical mixture of D-Cycloserine and Levofloxacin, were loaded into mesoporous nanoparticles. The nanoparticles were characterized (SEM, FTIR, NMR, particle size, zeta potential, PDI, %EE), and evaluated for in vitro drug release, in vivo pharmacokinetic behavior, and in vitro activity against M. tuberculosis H37Rv. Results: Mesoporous nanoparticles demonstrated favorable characteristics for drug delivery. Notably, nanoparticles loaded with DSL exhibited more sustained drug release. In vitro microbiological studies showed that dual-drug conjugates, particularly DSL-loaded nanoparticles, exhibited superior synergistic activity against M. tuberculosis H37Rv compared to the physical mixture. Conclusion: Mesoporous nanoparticles provide a promising platform for the ratiometric and controlled delivery of D-Cycloserine and Levofloxacin. Conjugation with SCL offers a potential advantage for sustained drug release and enhanced efficacy in MDR-TB treatment compared to CAC conjugates and the physical drug mixture. Mesoporous nanoparticles Dual-drug conjugates D-Cycloserine Levofloxacin Chloroacetyl chloride Succinyl chloride Ratiometric delivery Controlled release MDR-TB M. tuberculosis H37Rv Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6422681","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":441580500,"identity":"9154bf32-3707-4af9-a10c-88d63605fee2","order_by":0,"name":"Nagashubha B","email":"","orcid":"","institution":"Manipal Academy of Higher Education","correspondingAuthor":false,"prefix":"","firstName":"Nagashubha","middleName":"","lastName":"B","suffix":""},{"id":441580501,"identity":"526d0b3b-ac3c-427f-8255-f2745cdb767c","order_by":1,"name":"Dr. Padmanabha Reddy Y","email":"","orcid":"","institution":"Raghavendra Institute of Pharmaceutical Education and Research","correspondingAuthor":false,"prefix":"Dr.","firstName":"Padmanabha","middleName":"Reddy","lastName":"Y","suffix":""},{"id":441580502,"identity":"1bbb187e-25c9-4c1a-a264-fc8c9c8cf6f1","order_by":2,"name":"Azger Dusthackeer VN","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Azger","middleName":"Dusthackeer","lastName":"VN","suffix":""},{"id":441580503,"identity":"8e1984e3-87af-4aaf-a2c2-e83eacb88de6","order_by":3,"name":"Dr. Lalit kumar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABD0lEQVRIiWNgGAWjYBACPgbmhgMMB6C8BCDmBzMKcGthY2BsOHAAWYtkA4hhgF8LA1wLCBiAOfi0sB9sPPzhzOFo/tkH2B483GGTb3x+deKHBwYM8vxiB7Br4UkEOuzG4dwZ5xLYDRLPpFluu/F2swTQYYYzZyfgcBhIy4fDuQ1nGNgkEtsOG5jdOLsBpCXB4DYOLfwPIVrmQ7T8NzCecXbzD7xaJKAO2wDRcsDAgL93G35bJIC2nDmTnrvxDGObROKZZAOJG7zbLBIMJHD6hZ8/+fCHimPWufPOMB+T/LnDzoC//+zmmz8qbOT5pbFrQQLACAIiBgYJsEoJQsoRuoAWHyBS9SgYBaNgFIwUAADCQ2vUdBaAigAAAABJRU5ErkJggg==","orcid":"","institution":"","correspondingAuthor":true,"prefix":"Dr.","firstName":"Lalit","middleName":"","lastName":"kumar","suffix":""}],"badges":[],"createdAt":"2025-04-10 18:53:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6422681/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6422681/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":81834627,"identity":"d01f91a3-43c6-4c49-b607-3d991eca6710","added_by":"auto","created_at":"2025-05-02 14:32:05","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2942683,"visible":true,"origin":"","legend":"","description":"","filename":"researcharticlelevocycloset.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6422681/v1_covered_e452381e-0bcf-41b5-8aea-1f11a01b70d5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mesoporous Nanoparticle-Mediated Ratio-metric \u0026 Controlled Release of D-Cycloserine and Levofloxacin: Comparing Chloroacetyl Chloride and Succinyl Chloride Conjugates with Physical Mixture for MDR Tuberculosis Treatment ","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Mesoporous nanoparticles, Dual-drug conjugates, D-Cycloserine, Levofloxacin, Chloroacetyl chloride, Succinyl chloride, Ratiometric delivery, Controlled release, MDR-TB, M. tuberculosis H37Rv","lastPublishedDoi":"10.21203/rs.3.rs-6422681/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6422681/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e The treatment of multi-drug-resistant tuberculosis (MDR-TB) is complicated by resistance to multiple anti-tubercular drugs. This study explores a mesoporous nanoparticle-based approach for the ratiometric and controlled delivery of D-Cycloserine and Levofloxacin to combat MDR-TB.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e To synthesize, characterize, and compare the efficacy of mesoporous nanoparticles loaded with D-Cycloserine and Levofloxacin conjugates, using Chloroacetyl Chloride (CAC) and Succinyl Chloride (SCL) as cross-linkers, against a physical mixture for MDR-TB treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Two dual-drug conjugates were synthesized: D-Cycloserine-Chloroacetyl Chloride-Levofloxacin (DCL) and D-Cycloserine-Succinyl Chloride-Levofloxacin (DSL). The conjugates' stability was assessed via hydrolysability testing. Both conjugates, along with a physical mixture of D-Cycloserine and Levofloxacin, were loaded into mesoporous nanoparticles. The nanoparticles were characterized (SEM, FTIR, NMR, particle size, zeta potential, PDI, %EE), and evaluated for in vitro drug release, in vivo pharmacokinetic behavior, and in vitro activity against \u003cem\u003eM. tuberculosis\u003c/em\u003e H37Rv.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Mesoporous nanoparticles demonstrated favorable characteristics for drug delivery. Notably, nanoparticles loaded with DSL exhibited more sustained drug release. In vitro microbiological studies showed that dual-drug conjugates, particularly DSL-loaded nanoparticles, exhibited superior synergistic activity against \u003cem\u003eM. tuberculosis\u003c/em\u003e H37Rv compared to the physical mixture.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Mesoporous nanoparticles provide a promising platform for the ratiometric and controlled delivery of D-Cycloserine and Levofloxacin. Conjugation with SCL offers a potential advantage for sustained drug release and enhanced efficacy in MDR-TB treatment compared to CAC conjugates and the physical drug mixture.\u003c/p\u003e","manuscriptTitle":"Mesoporous Nanoparticle-Mediated Ratio-metric \u0026amp; Controlled Release of D-Cycloserine and Levofloxacin: Comparing Chloroacetyl Chloride and Succinyl Chloride Conjugates with Physical Mixture for MDR Tuberculosis Treatment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-14 07:34:24","doi":"10.21203/rs.3.rs-6422681/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fea6d4ca-3414-4790-8556-251924260259","owner":[],"postedDate":"April 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-02T14:23:47+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-14 07:34:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6422681","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6422681","identity":"rs-6422681","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}