Structure-Dependent Incorporation of Terpenes into Amphiphilic Poly(2-oxazoline) Micelles

Structure-Dependent Incorporation of Terpenes into Amphiphilic Poly(2-oxazoline) Micelles | 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 Structure-Dependent Incorporation of Terpenes into Amphiphilic Poly(2-oxazoline) Micelles Liubov Palchak, Seraphim Kozlov, Alexander V. Kabanov This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9117735/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Poly(2‑oxazoline) (POx) amphiphilic block copolymers are highly effective carriers for poorly water‑soluble small molecules, yet structural features that promote drug incorporation remain unclear. Motivated by the unusually high loading of diterpene taxanes in POx micelles, we examined whether shared terpene motifs support solubilization with POx. Representative mono‑, di‑, and triterpenes,α‑pinene, carnosic acid (CA), carnosol (CARN), squalene, lupeol, betulin, and ursolic acid,were tested for micellization with a well‑defined POx triblock copolymer. Only the diterpenes formed small, uniform, and stable micelles. CA and CARN showed the best performance: CA produced reproducible 22–29 nm micelles at a 2/10 (w/w) CA/polymer feed, achieving ~17% loading capacity with quantitative efficiency. Higher feed ratios yielded large, polydisperse aggregates by DLS and TEM. Other terpenes displayed minimal or unstable incorporation. CA‑loaded micelles remained colloidally stable for 48 h at room temperature, though CA’s chemical stability varied by batch. Lyophilization improved CA stability, enabling 67–89% recovery after reconstitution. pH‑dependent studies showed increasing particle size with higher pH for CA/POx micelles, consistent with CA ionization and altered hydrogen bonding. Physiological NaCl suppressed this pH sensitivity for CA, indicating ionic‑strength‑mediated stabilization. Overall, the rigid diterpene scaffold and ortho‑hydroxyl groups appear key for POx incorporation, highlighting CA as a promising candidate for further formulation development. Amphiphilic triblock Poly(2-oxazoline) terpenes carnosic acid polymeric micelles Figures Figure 2 Full Text Additional Declarations No competing interests reported. Supplementary Files Suplementfugures.pdf SupplementaryinformationCApaper.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 29 Mar, 2026 Reviews received at journal 29 Mar, 2026 Reviews received at journal 27 Mar, 2026 Reviewers agreed at journal 21 Mar, 2026 Reviewers agreed at journal 19 Mar, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviewers agreed at journal 16 Mar, 2026 Reviewers agreed at journal 16 Mar, 2026 Reviewers invited by journal 16 Mar, 2026 Editor assigned by journal 16 Mar, 2026 Submission checks completed at journal 16 Mar, 2026 First submitted to journal 13 Mar, 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. 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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-9117735","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":607393652,"identity":"fb1a9ba7-a889-4e2b-818e-d58e1bd31ff6","order_by":0,"name":"Liubov Palchak","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAmklEQVRIiWNgGAWjYBACPgYGxgMfIGwD4rSwAfHBGSRrOcxDmhbp5geHbdvuyDOwN2+TIE6LzDGDw7ltzwwbeI6VEalFIgGk5XACg0SOGbFa0j8ctgRpkX9DtJYcg8OMYFt4iNUic6bgYM+5w4ZtPGnFFkRp4Zdu3/jgR9lheX72wxtvEKWFAeYYNuKUI2sZBaNgFIyCUYATAABSVCpFOBHNBgAAAABJRU5ErkJggg==","orcid":"","institution":"University of North Carolina at Chapel Hill","correspondingAuthor":true,"prefix":"","firstName":"Liubov","middleName":"","lastName":"Palchak","suffix":""},{"id":607393653,"identity":"90b00661-e809-4d7a-99c6-ab68bd4121b4","order_by":1,"name":"Seraphim Kozlov","email":"","orcid":"","institution":"University of North Carolina at Chapel Hill","correspondingAuthor":false,"prefix":"","firstName":"Seraphim","middleName":"","lastName":"Kozlov","suffix":""},{"id":607393654,"identity":"2f022db8-42b1-4185-81cf-ea7ed5d05461","order_by":2,"name":"Alexander V. 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