Modeling thixotropic hydrogel carriers to limit healthy-tissue exposure via localized drug retention in chemotherapy

Brojan, Miha (author), Komic, Jacopo (author), Istenič, Enej (author)

In this work, we develop a coupled multiphysics model that integrates polymer carriers exhibiting time-dependent thixotropic structural recovery with Darcy flow, linear Biot poroelasticity and advection–diffusion transport in a spherically symmetric, isotropic and homogeneous tissue domain. The formulation explicitly links rheological evolution to pressure-driven flow, interstitial deformation and solute transport through a unified framework, enabling systematic prediction of post-injection behavior. Unlike conventional approaches that assume constant carrier properties, the present model incorporates a time-dependent viscosity evolution, capturing the transition from an initially shear-thinned state to a recovered, highly viscous structure. Numerical simulations using hydroxypropyl methylcellulose and methotrexate parameters as representative components demonstrate that rapid post-injection viscosity recovery suppresses pressure-driven transport and diffusion, thereby enhancing local drug retention near the injection site. A systematic sensitivity analysis identifies the equilibrium viscosity as the dominant parameter controlling spatial localization, whereas tissue mechanical properties exert a comparatively minor influence. An effectiveness metric based on the Kullback–Leibler divergence reveals a tumor-size-dependent trade-off between spatial coverage and retention. The proposed framework thus introduces a predictive tool for analyzing coupled rheological-transport interactions and for the rational design and optimization of thixotropy-enhanced local chemotherapy strategies.

• Language: English
• Keywords: coupled multiphysics model, thixotropy, Biot poroelastic medium, Darcy’s law, advection - diffusion, spherical symmetry, hydroxypropyl methylcellulose, HPMC, methotrexate, MTX
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FS - Faculty of Mechanical Engineering
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 23 str.
• Numbering: Vol. 18, iss. 14, art. 1704
• PID: 20.500.12556/RUL-184692
• UDC: 532.135
• ISSN on article: 2073-4360
• DOI: 10.3390/polym18141704
• COBISS.SI-ID: 284508419
• Publication date in RUL: 13.07.2026

Record is a part of a journal

• Title: Polymers
• Shortened title: Polymers
• Publisher: MDPI AG
• ISSN: 2073-4360
• COBISS.SI-ID: 517951257

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: povezani multifizikalni modeli, tiksotropija, Biotova poroelastičnost, Darcyev zakon, mehanika fluidov, sferična simetrija, hidroksipropil metilceluloza, metotreksat

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: J2-2499
• Name: Razvoj kvazi-periodičnih deformacijskih vzorcev v viskoelastičnih strukturah