Multiphysics Simulation of Liposome Release from Hydrogels for Cavity Filling Following Patient-Specific Breast Tumor Surgery.

IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutical Sciences Pub Date : 2024-11-19 DOI:10.1016/j.ejps.2024.106966
Álvaro González-Garcinuño, Antonio Tabernero, Celia Nieto, Eva Martín Del Valle, Sasa Kenjeres
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Abstract

Several studies have recommended the use of hydrogels for localized targeted delivery of chemotherapeutic drugs following tumor removal surgery. This approach aims to both fill the cavity and prevent cancer recurrence. The use of Multiphysics-based simulation emerges as a valuable strategy for minimizing experimental work, providing detailed insights into how drug release occurs in the tissue, and enabling the optimization of the design. In this study, we introduced a mathematical model, utilizing experimental data, to investigate the transport of liposomes carrying MZ1 from a thermosensitive hydrogel and their impact on the viability of breast cancer cells. The proposed comprehensive model considers not just the transport within the interstitial tissue, represented as a porous medium, but also the uptake by cells and its influence on cell viability, along with the potential lymphatic drainage. The six real patient-specific tumor shapes extracted from MRI scans were used to investigate how the size and form of the tumor can modify the transport pattern. The computational results revealed that the concentration of liposomes in the tissue is significantly influenced by their release from the hydrogel, which proved to be the limiting step. Liposome concentrations of approximately 0.1% weight were found to be sufficient in ensuring minimal cell survival in the vicinity of the tumor.

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针对患者乳腺肿瘤手术后腔隙填充从水凝胶中释放脂质体的多物理场模拟
一些研究建议在肿瘤切除手术后使用水凝胶局部靶向输送化疗药物。这种方法既能填充空腔,又能防止癌症复发。使用基于多物理场的模拟是一种有价值的策略,可最大限度地减少实验工作,详细了解药物在组织中的释放过程,并优化设计。在本研究中,我们利用实验数据引入了一个数学模型,研究携带 MZ1 的脂质体从热敏水凝胶中的传输及其对乳腺癌细胞活力的影响。所提出的综合模型不仅考虑了作为多孔介质的间质组织内的传输,还考虑了细胞的吸收及其对细胞活力的影响,以及潜在的淋巴引流。我们利用从核磁共振扫描中提取的六种真实的特定患者肿瘤形状来研究肿瘤的大小和形态如何改变传输模式。计算结果显示,脂质体在组织中的浓度受其从水凝胶中释放的影响很大,这被证明是限制性步骤。研究发现,脂质体的浓度约为 0.1%,足以确保肿瘤附近的细胞存活率最低。
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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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