Amitriptyline-Loaded Polyvinyl Pyrrolidone Nano Formulation For The Management Of Nitroglycerin-Induced Migraine In Mice

Amitriptyline-Loaded Polyvinyl Pyrrolidone Nano Formulation For The Management Of Nitroglycerin-Induced Migraine In Mice | 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 Amitriptyline-Loaded Polyvinyl Pyrrolidone Nano Formulation For The Management Of Nitroglycerin-Induced Migraine In Mice Shraman Kumar Bohra, Tafadzwa Justin Chiome, Jérôme Laurin, Christophe Pellegrino, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7459994/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Apr, 2026 Read the published version in Discover Neuroscience → Version 1 posted 18 You are reading this latest preprint version Abstract Migraine is a globally prevalent neurological disorder affecting mostly individuals within the 19–49 age group, while being more prevalent in women. Amitriptyline, a tricyclic antidepressant, is used as a prophylactic treatment. However, its first-line use remains controversial due to side effects and reduced efficacy over time. This study focused on developing a nano-formulation of amitriptyline encapsulated in a PVP polymer matrix to enhance its stability, brain uptake, and therapeutic efficacy. The resulting formulation exhibited controlled drug release with an early onset. Behavioural studies in nitroglycerin-induced migraine mice demonstrated a significant reduction in photophobia and freezing behaviour. Biochemical analysis confirmed migraine onset through increased lactic acid and glutamate levels, which decreased post-treatment, indicating the nano-formulation’s effectiveness in mitigating glutamate excitotoxicity even at low doses. Histopathological examination of the cortex and trigeminal nucleus caudalis showed no signs of cytotoxic damage, demonstrating the formulation’s biocompatibility. These findings highlight the potential of nano-based drug delivery systems to improve amitriptyline’s pharmacokinetics, ensuring better brain penetration while minimizing systemic side effects. Overcoming the challenges posed by the blood-brain barrier, this approach could lead to safer and more effective treatments for migraine. Further research is required to translate these findings into clinical applications. amitriptyline controlled drug release migraine nanoparticles neuroinflammation Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 04 Apr, 2026 Read the published version in Discover Neuroscience → Version 1 posted Editorial decision: Revision requested 13 Oct, 2025 Reviews received at journal 06 Oct, 2025 Reviews received at journal 04 Oct, 2025 Reviewers agreed at journal 01 Oct, 2025 Reviews received at journal 30 Sep, 2025 Reviewers agreed at journal 29 Sep, 2025 Reviews received at journal 28 Sep, 2025 Reviews received at journal 23 Sep, 2025 Reviewers agreed at journal 23 Sep, 2025 Reviewers agreed at journal 22 Sep, 2025 Reviewers agreed at journal 18 Sep, 2025 Reviewers agreed at journal 18 Sep, 2025 Reviewers agreed at journal 18 Sep, 2025 Reviewers invited by journal 18 Sep, 2025 Editor invited by journal 11 Sep, 2025 Editor assigned by journal 30 Aug, 2025 Submission checks completed at journal 30 Aug, 2025 First submitted to journal 26 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. 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-7459994","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":521653748,"identity":"6c9b60d4-39c8-4b0c-888b-629cf949cede","order_by":0,"name":"Shraman Kumar Bohra","email":"","orcid":"","institution":"University of Helsinki","correspondingAuthor":false,"prefix":"","firstName":"Shraman","middleName":"Kumar","lastName":"Bohra","suffix":""},{"id":521653749,"identity":"b0d004e9-9f13-4bba-ab67-8c2f58502615","order_by":1,"name":"Tafadzwa Justin Chiome","email":"","orcid":"","institution":"JSS Academy of Higher Education \u0026 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Amitriptyline, a tricyclic antidepressant, is used as a prophylactic treatment. However, its first-line use remains controversial due to side effects and reduced efficacy over time. This study focused on developing a nano-formulation of amitriptyline encapsulated in a PVP polymer matrix to enhance its stability, brain uptake, and therapeutic efficacy. The resulting formulation exhibited controlled drug release with an early onset.\u003c/p\u003e\u003cp\u003eBehavioural studies in nitroglycerin-induced migraine mice demonstrated a significant reduction in photophobia and freezing behaviour. Biochemical analysis confirmed migraine onset through increased lactic acid and glutamate levels, which decreased post-treatment, indicating the nano-formulation\u0026rsquo;s effectiveness in mitigating glutamate excitotoxicity even at low doses. Histopathological examination of the cortex and trigeminal nucleus caudalis showed no signs of cytotoxic damage, demonstrating the formulation\u0026rsquo;s biocompatibility. These findings highlight the potential of nano-based drug delivery systems to improve amitriptyline\u0026rsquo;s pharmacokinetics, ensuring better brain penetration while minimizing systemic side effects. Overcoming the challenges posed by the blood-brain barrier, this approach could lead to safer and more effective treatments for migraine. Further research is required to translate these findings into clinical applications.\u003c/p\u003e","manuscriptTitle":"Amitriptyline-Loaded Polyvinyl Pyrrolidone Nano Formulation For The Management Of Nitroglycerin-Induced Migraine In Mice","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-01 17:38:23","doi":"10.21203/rs.3.rs-7459994/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-13T10:03:52+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-06T05:31:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-04T07:13:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"276814983683832082736273234870404117187","date":"2025-10-02T02:18:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-01T01:09:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"70156939963877070809690599388603002429","date":"2025-09-29T16:21:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-29T03:17:08+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-23T10:18:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"189305104182485866396667985977519590487","date":"2025-09-23T05:19:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"24000101267547210365071629999006982470","date":"2025-09-22T15:32:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"36293781947741759375931350895101755267","date":"2025-09-19T03:13:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"313225486828980961317769427693334147028","date":"2025-09-18T13:29:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"21246720013045535629820990100116353282","date":"2025-09-18T04:08:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-18T04:03:15+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-11T07:19:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-30T05:14:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-30T05:13:22+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Neuroscience","date":"2025-08-26T07:29:25+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-neuroscience","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ndev","sideBox":"Learn more about [Neural Development](http://neuraldevelopment.biomedcentral.com/)","snPcode":"13064","submissionUrl":"https://submission.nature.com/new-submission/13064/3","title":"Discover Neuroscience","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3ecca295-3ce4-4cda-9a72-be2c703b00d9","owner":[],"postedDate":"October 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-07T16:16:52+00:00","versionOfRecord":{"articleIdentity":"rs-7459994","link":"https://doi.org/10.1186/s13064-026-00238-9","journal":{"identity":"discover-neuroscience","isVorOnly":false,"title":"Discover Neuroscience"},"publishedOn":"2026-04-04 15:59:00","publishedOnDateReadable":"April 4th, 2026"},"versionCreatedAt":"2025-10-01 17:38:23","video":"","vorDoi":"10.1186/s13064-026-00238-9","vorDoiUrl":"https://doi.org/10.1186/s13064-026-00238-9","workflowStages":[]},"version":"v1","identity":"rs-7459994","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7459994","identity":"rs-7459994","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}