Multi-physics numerical simulation study on thermo-sensitive gel delivery for a local post-tumor surgery treatment

• Published in: European journal of pharmaceutical sciences 2024-12, Vol.203, p.106917, Article 106917
• Main Authors: González-Garcinuño, Álvaro, Tabernero, Antonio, Blanco-López, Marcos, Martín del Valle, Eva, Kenjeres, Sasa
• Format: Article
• Language: English
• Subjects: Gelation; Injection; Level set method; Multi-physics simulations; Thermo-responsive hydrogel
• ISSN: 0928-0987; 1879-0720; 1879-0720
• DOI: 10.1016/j.ejps.2024.106917

Numerous studies in the literature have proposed the use of thermo-responsive hydrogels for filling cavities after tumor resection. However, optimizing the injection process is challenging due to the complex interplay of various multi-physics phenomena, such as the coupling of flow and heat transfer, multi-phase interactions, and phase-change dynamics. Therefore, gaining a fundamental understanding of these processes is crucial. In this study, we introduce a thermo-sensitive hydrogel formulated with poloxamer 407 and Gellan gum as a promising filling agent, offering an ideal phase-transition temperature along with suitable elastic and viscous modulus properties. We performed multi-physics simulations to predict the flow and temperature distributions during hydrogel injection. The results suggested that the hydrogel should be kept at 4 °C and injected within 90 s to avoid reaching the transition temperature. Cavity filling simulations indicated a symmetric distribution of the hydrogel, with minimal influence from the syringe's position. The temperature gradient at the cavity edge delays gelation during injection, which is essential to guarantee its administration as a liquid. The hydrogel's viscosity follows a sigmoidal function relative to temperature, taking five minutes to reach its maximum value. In summary, the multi-physics simulations carried out in this study confirm the potential of thermo-responsive hydrogels for use in post-tumor surgery treatment and define the conditions for a proper administration. Furthermore, the proposed model can be widely applied to other thermo-responsive hydrogels or under different conditions. [Display omitted]