Mechanistic model of phase-transitioning therapeutics injected into poroelastic tissue for improved targeting of superficial tumors

Mechanistic model of phase-transitioning therapeutics injected into poroelastic tissue for improved targeting of superficial tumors | 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 Article Mechanistic model of phase-transitioning therapeutics injected into poroelastic tissue for improved targeting of superficial tumors Daniel R. Adrianzen Alvarez, Eva S. Landeta Orozco, Nimmi Ramanujam, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7900123/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Feb, 2026 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract The development of new drugs and drug delivery systems relies heavily on careful acquisition and interpretation of large amounts of experimental data, to identify and select promising candidates for therapeutic and prophylactic use. Predictive mathematical modeling can expedite this process by capturing the complex interplay of physical, chemical and biological factors that influence drug delivery. However, traditional compartmental models of pharmacokinetics and pharmacodynamics typically rely on oversimplified approximations of drug transport mechanisms and may fail to accurately represent the key deterministic processes that drive drug mass transport - particularly in complex delivery scenarios where the drug targets are close to the sites of drug administration. Here, we present a deterministic mathematical framework that addresses a challenging drug delivery modality: the injection of a fluid drug vehicle that undergoes phase separation upon entering poroelastic tissue. This phase change improves localized retention of the loaded drug in a finite volume near the injection site. Our model is directly relevant to in situ-gelling injections of chemotherapeutic agents into superficial tumors - a strategy gaining attention in the development of improved cancer therapeutics. Our approach uniquely incorporates both diffusion and convection, accounts for tissue poroelasticity, and uses Cahn-Hilliard theory to describe the phase separation behavior of the injected material. Simulations across a broad parameter space indicate that drug retention is enhanced in softer tissues and with high-rate, low-volume injections. This computational framework is currently being used to guide the design of improved therapeutic strategies for ethanol-based ablation, when co-injected with ethyl cellulose as a phase-transitioning agent for superficial tumors. Biological sciences/Cancer Biological sciences/Computational biology and bioinformatics Biological sciences/Drug discovery Physical sciences/Mathematics and computing Intratumoral injection phase transitioning therapeutic drug delivery injection delivery parameters mechanistic modeling Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 24 Feb, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 15 Dec, 2025 Reviews received at journal 13 Dec, 2025 Reviews received at journal 13 Dec, 2025 Reviewers agreed at journal 11 Dec, 2025 Reviewers agreed at journal 04 Dec, 2025 Reviewers invited by journal 03 Dec, 2025 Editor invited by journal 24 Oct, 2025 Editor assigned by journal 22 Oct, 2025 Submission checks completed at journal 22 Oct, 2025 First submitted to journal 19 Oct, 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-7900123","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":555286837,"identity":"e1110f7d-9869-4b19-8238-f52495be6441","order_by":0,"name":"Daniel R. 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