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

IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutical Sciences Pub Date : 2024-09-28 DOI:10.1016/j.ejps.2024.106917
Álvaro González-Garcinuño , Antonio Tabernero , Marcos Blanco-López , Eva Martín del Valle , Sasa Kenjeres
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Abstract

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.

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用于肿瘤术后局部治疗的热敏凝胶输送多物理场数值模拟研究
许多文献研究都提出使用热响应水凝胶来填充肿瘤切除后的空腔。然而,由于各种多物理现象的复杂相互作用,如流动与传热的耦合、多相相互作用和相变动力学,优化注射过程具有挑战性。因此,从根本上了解这些过程至关重要。在本研究中,我们介绍了一种热敏水凝胶,它由聚氧乙烯-407 和结冷胶配制而成,是一种很有前景的填充剂,具有理想的相变温度以及合适的弹性和粘性模量特性。我们进行了多物理场模拟,以预测水凝胶注射过程中的流动和温度分布。结果表明,水凝胶应保持在 4°C,并在 90 秒内注入,以避免达到转变温度。空腔填充模拟表明,水凝胶呈对称分布,注射器位置的影响极小。空腔边缘的温度梯度延迟了注射过程中的凝胶化,这对于保证水凝胶作为液体给药至关重要。水凝胶的粘度随温度变化呈曲线函数关系,五分钟后达到最大值。总之,本研究中进行的多物理场模拟证实了热响应水凝胶在肿瘤术后治疗中的应用潜力,并确定了适当给药的条件。此外,所提出的模型可广泛应用于其他热响应水凝胶或不同条件下。
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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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