Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden; Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
Eur J Pharm Sci. 2022 May 1;172:106150. doi: 10.1016/j.ejps.2022.106150. Epub 2022 Feb 26.
Hydrogels of varying complexity are routinely used as scaffolds and 3D structures for in vitro tumor models to increase physiological relevance within pre-clinical cancer research. Relatively simple hydrogels such as agarose are well characterised, meanwhile biomimetic gels containing collagen and fibrin(ogen) have been studied to a much lesser extent. In this study, hydrogels mimicking the biophysical characteristics of liver cancer progression were investigated in terms of their UV-properties and influence on diffusion coefficients of different substances. UV-imaging technology was used to both visualize and quantify the diffusion process in a simple and rapid way. In general, agarose gel diffusion agreed well with predictions using the Stokes-Einstein equation meanwhile the biomimetic gels reduced diffusion coefficients by up to 70%. For doxorubicin, spatio-temporal tissue concentration modelling was used to translate in vitro diffusion to the more clinical context of tumor penetration in a solid liver tumor supplied by arterial blood.
水凝胶的复杂程度不同，通常被用作体外肿瘤模型的支架和 3D 结构，以提高临床前癌症研究中的生理相关性。相对简单的水凝胶，如琼脂糖，已经得到了很好的描述，而仿生凝胶，如含有胶原蛋白和纤维蛋白原的凝胶，则研究得较少。在这项研究中，研究人员研究了模拟肝癌进展的生物物理特性的水凝胶，考察了它们的 UV 特性及其对不同物质扩散系数的影响。UV 成像技术被用于以简单和快速的方式可视化和量化扩散过程。一般来说，琼脂糖凝胶的扩散与使用 Stokes-Einstein 方程的预测非常吻合，而仿生凝胶的扩散系数降低了 70%。对于多柔比星，时空组织浓度建模用于将体外扩散转化为更具临床意义的实体肝肿瘤在动脉血供应下的肿瘤穿透情况。
