Department of Nanoengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Angew Chem Int Ed Engl. 2021 Aug 23;60(35):19074-19078. doi: 10.1002/anie.202106674. Epub 2021 Jul 19.
Levodopa (L-Dopa) is the "gold-standard" medication for symptomatic therapy of Parkinson disease (PD). However, L-Dopa long-term use is associated with the development of motor and non-motor complications, primarily due to its fluctuating plasma levels in combination with the disease progression. Herein, we present the first example of individualized therapeutic drug monitoring for subjects upon intake of standard L-Dopa oral pill, centered on dynamic tracking of the drug concentration in naturally secreted fingertip sweat. The touch-based non-invasive detection method relies on instantaneous collection of fingertip sweat on a highly permeable hydrogel that transports the sweat to a biocatalytic tyrosinase-modified electrode, where sweat L-Dopa is measured by reduction of the dopaquinone enzymatic product. Personalized dose-response relationship is demonstrated within a group of human subjects, along with close pharmacokinetic correlation between the finger touch-based fingertip sweat and capillary blood samples.
左旋多巴(L-Dopa)是治疗帕金森病(PD)症状的“金标准”药物。然而,L-Dopa 的长期使用与运动和非运动并发症的发展有关,主要是由于其血浆水平波动,加上疾病的进展。在此,我们介绍了首例以标准 L-Dopa 口服丸剂为基础,对受试者进行个体化治疗药物监测的实例,其重点是对自然分泌的指尖汗液中药物浓度的动态跟踪。基于触摸的无创检测方法依赖于对手指尖汗液的即时采集,汗液被收集在高渗透性水凝胶上,水凝胶将汗液输送到生物催化酪氨酸酶修饰的电极,在电极上通过还原多巴醌酶促产物来测量汗液中的 L-Dopa。在一组人体受试者中证明了个性化的剂量反应关系,并且指尖汗液与毛细血管血样之间存在密切的药代动力学相关性。