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

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

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.

• Jezik: Angleški jezik
• Ključne besede: coupled multiphysics model, thixotropy, Biot poroelastic medium, Darcy’s law, advection - diffusion, spherical symmetry, hydroxypropyl methylcellulose, HPMC, methotrexate, MTX
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FS - Fakulteta za strojništvo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 23 str.
• Številčenje: Vol. 18, iss. 14, art. 1704
• PID: 20.500.12556/RUL-184692
• UDK: 532.135
• ISSN pri članku: 2073-4360
• DOI: 10.3390/polym18141704
• COBISS.SI-ID: 284508419
• Datum objave v RUL: 13.07.2026

Gradivo je del revije

• Naslov: Polymers
• Skrajšan naslov: Polymers
• Založnik: MDPI AG
• ISSN: 2073-4360
• COBISS.SI-ID: 517951257

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: povezani multifizikalni modeli, tiksotropija, Biotova poroelastičnost, Darcyev zakon, mehanika fluidov, sferična simetrija, hidroksipropil metilceluloza, metotreksat

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: J2-2499
• Naslov: Razvoj kvazi-periodičnih deformacijskih vzorcev v viskoelastičnih strukturah