Empa, Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Biomimetic Membranes and Textiles, Lerchenfeldstrasse 5, CH-9014, St. Gallen, Switzerland.
University of Bern, ARTORG Center for Biomedical Engineering Research, Mittelstrasse 43, CH-3012, Bern, Switzerland.
Drug Deliv Transl Res. 2023 Sep;13(9):2272-2285. doi: 10.1007/s13346-023-01305-y. Epub 2023 Mar 10.
Fentanyl transdermal therapy is a suitable treatment for moderate-to-severe cancer-related pain. The inter-individual variability of the patients leads to different therapy responses. This study aims to determine the effect of physiological features on the achieved pain relief. Therefore, a set of virtual patients was developed by using Markov chain Monte Carlo (MCMC) based on actual patient data. The members of this virtual population differ by age, weight, gender, and height. Tailored digital twins were developed using these correlated, individualized parameters to propose a personalized therapy for each patient. It was shown that patients of different ages, weights, and gender have significantly different fentanyl blood uptake, plasma fentanyl concentration, pain relief, and ventilation rate. In the digital twins, we included the virtual patients' response to the treatment, namely, pain relief. Therefore, the digital twin was able to adjust the therapy in silico to have more efficient pain relief. By implementing digital-twin-assisted therapy, the average pain intensity decreased by 16% compared to conventional therapy. The median time without pain increased by 23 h over 72 h. Therefore, the digital twin can be successfully used in individual control of transdermal therapy to reach higher pain relief and maintain steady pain relief. (Created with BioRender.com).
芬太尼透皮治疗是一种适用于中重度癌痛的治疗方法。由于患者之间存在个体差异，导致治疗效果也有所不同。本研究旨在确定生理特征对缓解疼痛的影响。因此，通过使用基于实际患者数据的马尔可夫链蒙特卡罗（MCMC）方法，开发了一组虚拟患者。该虚拟人群的成员在年龄、体重、性别和身高方面存在差异。使用这些相关的个体化参数开发定制的数字双胞胎，为每位患者提出个性化的治疗方案。结果表明，不同年龄、体重和性别的患者芬太尼血药浓度、血浆芬太尼浓度、疼痛缓解和通气率有显著差异。在数字双胞胎中，我们纳入了虚拟患者对治疗的反应，即疼痛缓解。因此，数字双胞胎能够在计算机中调整治疗方案，以实现更有效的疼痛缓解。与传统治疗相比，实施数字双胞胎辅助治疗后，平均疼痛强度降低了 16%。72 小时内无疼痛的中位数时间增加了 23 小时。因此，数字双胞胎可成功用于经皮治疗的个体化控制，以达到更高的疼痛缓解率并维持稳定的疼痛缓解。（由 BioRender.com 创建）。
