Preparation and In Vitro Sustained Release Performance of Thermosensitive Gel Microsphere Composite Loaded with Anti-Tuberculosis Drug PaMZ/BMP-2

Preparation and In Vitro Sustained Release Performance of Thermosensitive Gel Microsphere Composite Loaded with Anti-Tuberculosis Drug PaMZ/BMP-2 | 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 Preparation and In Vitro Sustained Release Performance of Thermosensitive Gel Microsphere Composite Loaded with Anti-Tuberculosis Drug PaMZ/BMP-2 Gui Li, Qianbo Song, Ye Song, Wenxing Liao, Dong Zhao, Binqing Hong, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7441834/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Jan, 2026 Read the published version in Journal of Orthopaedic Surgery and Research → Version 1 posted 20 You are reading this latest preprint version Abstract Objective To meet the needs of local treatment for spinal tuberculosis, this study developed a thermosensitive gel microsphere composite with both anti-tuberculosis and osteogenesis-promoting functions for efficient drug sustained release. The composite consists of anti-tuberculosis drugs (Pretomanid, Pa-824; Moxifloxacin, M; Pyrazinamide, Z) and bone morphogenetic protein-2 (BMP-2) to optimize drug release kinetics and enhance local therapeutic effects. Methods PaMZ/BMP-2 microspheres were prepared using microfluidics and characterized by SEM, particle size analysis, and XRD. LC-MS and ELISA measured drug and BMP-2 release. The thermosensitive gel (P407/P188) ratio was optimized to ensure it remained liquid at room temperature and formed a gel at 37°C for sustained release. Results Microspheres were spherical with an average size of 203.92 ± 27.76 µm. Encapsulation rates were 112.69%, 24.15%, and 15.18% for Pa, M, and Z, respectively. In vitro release showed Pa and M sustained release for over 17 days, with the gel prolonging drug release. Conclusion This study successfully prepared PaMZ/BMP-2 microspheres with good morphology and drug loading capacity, achieving controlled sustained release through thermosensitive gel. This provides a new strategy for local minimally invasive treatment of spinal tuberculosis and lays the foundation for subsequent in vivo experiments and clinical translation. Bone Regeneration Anti-Tuberculosis Drugs Smart Materials Microspheres Bone Morphogenetic Protein 2 Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 10 Jan, 2026 Read the published version in Journal of Orthopaedic Surgery and Research → Version 1 posted Editorial decision: Revision requested 17 Nov, 2025 Reviews received at journal 13 Nov, 2025 Reviews received at journal 12 Nov, 2025 Reviews received at journal 12 Nov, 2025 Reviews received at journal 26 Oct, 2025 Reviewers agreed at journal 20 Oct, 2025 Reviewers agreed at journal 17 Oct, 2025 Reviewers agreed at journal 16 Oct, 2025 Reviewers agreed at journal 16 Oct, 2025 Reviewers agreed at journal 15 Oct, 2025 Reviewers agreed at journal 15 Oct, 2025 Reviews received at journal 08 Oct, 2025 Reviews received at journal 06 Oct, 2025 Reviewers agreed at journal 10 Sep, 2025 Reviewers agreed at journal 08 Sep, 2025 Reviewers agreed at journal 08 Sep, 2025 Reviewers invited by journal 07 Sep, 2025 Editor assigned by journal 26 Aug, 2025 Submission checks completed at journal 26 Aug, 2025 First submitted to journal 23 Aug, 2025 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. 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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-7441834","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":513186242,"identity":"cbacb8a6-8466-4ac4-a5f7-670f06f2617b","order_by":0,"name":"Gui Li","email":"","orcid":"","institution":"The Second Affiliated Hospital of Zunyi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Gui","middleName":"","lastName":"Li","suffix":""},{"id":513186243,"identity":"387aadb6-cb0a-4114-8fc2-095c71d339e1","order_by":1,"name":"Qianbo Song","email":"","orcid":"","institution":"The Second Affiliated Hospital of Zunyi Medical 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The composite consists of anti-tuberculosis drugs (Pretomanid, Pa-824; Moxifloxacin, M; Pyrazinamide, Z) and bone morphogenetic protein-2 (BMP-2) to optimize drug release kinetics and enhance local therapeutic effects.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003ePaMZ/BMP-2 microspheres were prepared using microfluidics and characterized by SEM, particle size analysis, and XRD. LC-MS and ELISA measured drug and BMP-2 release. The thermosensitive gel (P407/P188) ratio was optimized to ensure it remained liquid at room temperature and formed a gel at 37\u0026deg;C for sustained release.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eMicrospheres were spherical with an average size of 203.92\u0026thinsp;\u0026plusmn;\u0026thinsp;27.76 \u0026micro;m. Encapsulation rates were 112.69%, 24.15%, and 15.18% for Pa, M, and Z, respectively. In vitro release showed Pa and M sustained release for over 17 days, with the gel prolonging drug release.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThis study successfully prepared PaMZ/BMP-2 microspheres with good morphology and drug loading capacity, achieving controlled sustained release through thermosensitive gel. This provides a new strategy for local minimally invasive treatment of spinal tuberculosis and lays the foundation for subsequent in vivo experiments and clinical translation.\u003c/p\u003e","manuscriptTitle":"Preparation and In Vitro Sustained Release Performance of Thermosensitive Gel Microsphere Composite Loaded with Anti-Tuberculosis Drug PaMZ/BMP-2","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-12 14:39:09","doi":"10.21203/rs.3.rs-7441834/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-18T01:37:07+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-13T14:40:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-12T20:11:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-12T17:17:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-26T16:40:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"257653502081900756193949812384880166393","date":"2025-10-20T05:18:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"239697834288016020253372978775989941128","date":"2025-10-17T05:22:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"30583620868160489362602784503155246632","date":"2025-10-17T03:44:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"239620460555804085103081008157311520039","date":"2025-10-16T09:07:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"113061375153376896058563527833532248238","date":"2025-10-15T15:30:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"42681252259729627371144660175761720670","date":"2025-10-15T04:43:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-08T10:49:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-06T14:18:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"48511985274730546207830083530477328359","date":"2025-09-10T14:59:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3352820262343678847916484512366479458","date":"2025-09-08T06:12:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"28052067680229497670901552264556828550","date":"2025-09-08T05:43:02+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-08T03:12:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-26T09:26:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-26T08:25:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Orthopaedic Surgery and Research","date":"2025-08-23T14:09:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-orthopaedic-surgery-and-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"josr","sideBox":"Learn more about [Journal of Orthopaedic Surgery and Research](http://josr-online.biomedcentral.com)","snPcode":"13018","submissionUrl":"https://submission.nature.com/new-submission/13018/3","title":"Journal of Orthopaedic Surgery and Research","twitterHandle":"@MSKmedBMC","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c994f869-2af3-4d47-be14-68ce1653fd1a","owner":[],"postedDate":"September 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-12T16:11:49+00:00","versionOfRecord":{"articleIdentity":"rs-7441834","link":"https://doi.org/10.1186/s13018-025-06595-1","journal":{"identity":"journal-of-orthopaedic-surgery-and-research","isVorOnly":false,"title":"Journal of Orthopaedic Surgery and Research"},"publishedOn":"2026-01-10 15:58:03","publishedOnDateReadable":"January 10th, 2026"},"versionCreatedAt":"2025-09-12 14:39:09","video":"","vorDoi":"10.1186/s13018-025-06595-1","vorDoiUrl":"https://doi.org/10.1186/s13018-025-06595-1","workflowStages":[]},"version":"v1","identity":"rs-7441834","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7441834","identity":"rs-7441834","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}