p-Nitrophenyl Palmitate-Functionalized Gold Nanoparticles as a pH-Responsive and Enzyme-Accessible Drug Delivery Platform

p-Nitrophenyl Palmitate-Functionalized Gold Nanoparticles as a pH-Responsive and Enzyme-Accessible Drug Delivery Platform | 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 p-Nitrophenyl Palmitate-Functionalized Gold Nanoparticles as a pH-Responsive and Enzyme-Accessible Drug Delivery Platform Muhittin Kulak, Canan Gulmez Samsa This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9277948/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Nanoparticles composed of casein, chitosan, albumin, and Au were designed and characterized using UV-Vis, FESEM, FTIR, XRD, and zeta-potential analyses. The nanomatrix exhibited high p-nitrophenyl palmitate (pNPP) adsorption (95.8%) and ibuprofen loading (88.7%), and over 48 hours, the system maintained substantial structural stability at pH 5.5 and 7.4, with approximately 89% of pNPP remaining bound within the matrix. The average particle size increased from ~ 9 to 40 nm after pNPP adsorption and ibuprofen loading. The cumulative release after 48 hours exceeded 88% under all tested pH conditions. Drug release was analyzed using the mechanistically relevant Korsmeyer-Peppas model, indicating anomalous transport at pH 7.4 (diffusion and polymer swelling) and Super Case II transport at pH 5.5 (polymer chain relaxation and matrix erosion). Lipase activity confirmed that pNPP remained accessible as a substrate, with 64% activity at pH 7.4 consistent with maximum swelling and anomalous transport, demonstrating effective enzyme penetration into the polymer network. At extreme pH conditions, the observed lipase activities were found to be associated with matrix instability, lipase-driven and AuNP-mediated nanozyme-like effects, as well as spontaneous hydrolysis of pNPP. In addition, the platform served as an effective substrate for lipase even in the 3rd cycle and exhibited high drug reloading capacity. This dual-function platform enables pH-sensitive and efficient controlled release of ibuprofen, serves as an enzymatically accessible substrate, and exhibits high biocompatibility with low cytotoxicity, laying the groundwork for future enzyme-triggered or stimulus-controlled smart nanocarriers. Gold nanoparticles protein-polysaccharide nanocarrier surface functionalization pH-responsive drug release ibuprofen (model lipophilic drug) Full Text Additional Declarations Tables are available in the Supplementary Files section. Figures are available in the Supplementary Files section. Supplementary Files Table1.docx Table2.docx Table3.docx Figures.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 17 Apr, 2026 Reviewers invited by journal 17 Apr, 2026 Editor invited by journal 13 Apr, 2026 Editor assigned by journal 06 Apr, 2026 First submitted to journal 02 Apr, 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. 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-9277948","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":624762922,"identity":"fca61376-3db0-4ceb-a573-8e9264369d3b","order_by":0,"name":"Muhittin Kulak","email":"","orcid":"","institution":"Igdir University: Igdir Universitesi","correspondingAuthor":false,"prefix":"","firstName":"Muhittin","middleName":"","lastName":"Kulak","suffix":""},{"id":624762923,"identity":"a0e5ffb8-8f2e-4da0-9d67-5a649d54df51","order_by":1,"name":"Canan Gulmez 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