Optimization of the Redox-Sensitive Doxorubicin Loaded Chitosan-based Nanoparticles by Box–Behnken Experimental Design

Optimization of the Redox-Sensitive Doxorubicin Loaded Chitosan-based Nanoparticles by Box–Behnken Experimental Design | 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 Short Report Optimization of the Redox-Sensitive Doxorubicin Loaded Chitosan-based Nanoparticles by Box–Behnken Experimental Design Mahsa Babaei, Soheila Kashanian, Zahra Salemi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3828026/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 Developing a satisfactory approach for delivering the chemotherapeutic drugs is one of the critical points in cancer treatment. Box–Behnken Design (BBD) is a Response Surface Methodology (RSM) that investigates the significant effects of various independent factors on dependent variables and also covers all potential effects of their interactions only by three levels of each factor. Methods and Results In this study, a Crosslinked Chitosan-L-Cysteine (Cs-Cys)/Tripolyphosphate (TPP) Nanoparticles (Cs-CysNPs) was synthesized to load Doxorubicin (DOX) (Cs-CysNPs-DOX) into a polymeric matrix as a promising redox responsive NP for breast cancer treatment. A statistical optimization by BBD was employed to examine the effects of the essential variables (CS-Cys concentration, TPP concentration, and Cs-Cys/TPP ratio) to optimize the Entrapment Efficiency (EE%) as the dependent variable. The optimized formulations with high EE% were obtained at middle levels of Cs-Cys concentration (1.25 mg/ml), Cs-Cys/TPP ratio (6:1) and high levels of the TPP concentration. The optimized Cs-CysNPs-DOX showed enhanced EE% and Drug Loading (DL%) compared to CsNPs. Also, they had an average hydrodynamic size of 144.55 nm and a Polydispersity Index (PDI) of 0.262, which showed a resealable size with sufficient PDI. Also, the final formulation of NPs had a positive zeta potential, which caused the high stability of the suspension. Conclusions Consequently, the optimized Cs-Cys NPs could be investigated as a suitable carrier for DOX entrapment and delivery to breast cancer cells. Experimental Design Box Benken Chitosan Nanoparticle Optimazation Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryDataMolecularBiologyReports1402.09.17.docx 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-3828026","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":264678014,"identity":"397408d5-949c-4437-bddf-1a8e16bdce84","order_by":0,"name":"Mahsa Babaei","email":"","orcid":"","institution":"Razi University","correspondingAuthor":false,"prefix":"","firstName":"Mahsa","middleName":"","lastName":"Babaei","suffix":""},{"id":264678015,"identity":"46c4affa-8bea-42e4-91a2-5953d7276444","order_by":1,"name":"Soheila Kashanian","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYBACgwMMbEBKAsRmfMDAcICwFsMGhBZmA6K0GDOAtYABmwRRWszYjz978HOHhbw5A/uzap6aO3L8DMwPH93Ao8WGJ8fcsPeMhOHOBh6z2zzHnhlLNrAZG+fg08KQwybB2ybBuOEAD9ttHrbDiSCGND4tZvzPn0n+bZOw33CA/Vkxzz8itBhLJJhJA20BqmQwY+ZtI0KL4Yw3ZtKybRLJQJXGknP7DhtLNhPwi8H59GeSb9vqbIEOe/jhzbfDcvzszQ8f49OCAPIPGJh4QAxmopRDAeMPUlSPglEwCkbBiAEA/E1KFe9CAQgAAAAASUVORK5CYII=","orcid":"","institution":"Razi University","correspondingAuthor":true,"prefix":"","firstName":"Soheila","middleName":"","lastName":"Kashanian","suffix":""},{"id":264678016,"identity":"399ef7c7-aff0-417b-ac68-92900c1d2e72","order_by":2,"name":"Zahra Salemi","email":"","orcid":"","institution":"Arak University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Zahra","middleName":"","lastName":"Salemi","suffix":""}],"badges":[],"createdAt":"2024-01-01 19:59:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3828026/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3828026/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49223984,"identity":"ed144a8c-08de-473c-90ab-2c7935b40096","added_by":"auto","created_at":"2024-01-05 13:39:19","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":804210,"visible":true,"origin":"","legend":"","description":"","filename":"MolecularBiologyReports1402.10.10.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3828026/v1_covered_ca149dc9-20a3-4a46-a8af-6c155adb7c27.pdf"},{"id":49145898,"identity":"1c530cbf-cf63-4de0-81d3-37589de38d02","added_by":"auto","created_at":"2024-01-03 19:59:34","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":88972,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryDataMolecularBiologyReports1402.09.17.docx","url":"https://assets-eu.researchsquare.com/files/rs-3828026/v1/380ba95a831cd26814e24860.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Optimization of the Redox-Sensitive Doxorubicin Loaded Chitosan-based Nanoparticles by Box–Behnken Experimental Design","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"Experimental Design, Box Benken, Chitosan, Nanoparticle, Optimazation","lastPublishedDoi":"10.21203/rs.3.rs-3828026/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3828026/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDeveloping a satisfactory approach for delivering the chemotherapeutic drugs is one of the critical points in cancer treatment. Box\u0026ndash;Behnken Design (BBD) is a Response Surface Methodology (RSM) that investigates the significant effects of various independent factors on dependent variables and also covers all potential effects of their interactions only by three levels of each factor.\u003c/p\u003e\u003ch2\u003eMethods and Results\u003c/h2\u003e \u003cp\u003eIn this study, a Crosslinked Chitosan-L-Cysteine (Cs-Cys)/Tripolyphosphate (TPP) Nanoparticles (Cs-CysNPs) was synthesized to load Doxorubicin (DOX) (Cs-CysNPs-DOX) into a polymeric matrix as a promising redox responsive NP for breast cancer treatment. A statistical optimization by BBD was employed to examine the effects of the essential variables (CS-Cys concentration, TPP concentration, and Cs-Cys/TPP ratio) to optimize the Entrapment Efficiency (EE%) as the dependent variable. The optimized formulations with high EE% were obtained at middle levels of Cs-Cys concentration (1.25 mg/ml), Cs-Cys/TPP ratio (6:1) and high levels of the TPP concentration. The optimized Cs-CysNPs-DOX showed enhanced EE% and Drug Loading (DL%) compared to CsNPs. Also, they had an average hydrodynamic size of 144.55 nm and a Polydispersity Index (PDI) of 0.262, which showed a resealable size with sufficient PDI. Also, the final formulation of NPs had a positive zeta potential, which caused the high stability of the suspension.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eConsequently, the optimized Cs-Cys NPs could be investigated as a suitable carrier for DOX entrapment and delivery to breast cancer cells.\u003c/p\u003e","manuscriptTitle":"Optimization of the Redox-Sensitive Doxorubicin Loaded Chitosan-based Nanoparticles by Box–Behnken Experimental Design","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-03 19:59:29","doi":"10.21203/rs.3.rs-3828026/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":"e5f551fc-b4db-413a-a0e2-fff33835f665","owner":[],"postedDate":"January 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-01-05T13:31:01+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-03 19:59:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3828026","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3828026","identity":"rs-3828026","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}