Microneedle patch based on molecular motor as a spatio-temporal controllable dosing strategy of L-DOPA for Parkinson’s disease

• A microneedle patch (MNP) was developed by two-step template replication method. • A near infrared light responsive molecular motor in microneedle is prepared. • The L-DOPA in the microneedle can be released in spatio-temporal controlled. • Microneedles drug delivery system have excellent transdermal efficiency. • NIR-triggered drug delivery microneedles successfully treat Parkinson’s disease. Controlling medication according to the condition has become a universal treatment regimen for Parkinson's disease (PD) worldwide. However, the general oral administration method is prone to a variety of digestive system discomfort, easy to be broken down by digestive juices and intestinal microorganisms, resulting in low absorption efficiency, and a serious delay in the efficacy of the drug. Here, we developed a microneedle patch (MNP) that could release drugs with controlled temporal and spatial precision triggered by near-infrared (NIR) light for the treatment of PD. The microneedles (MNs) took Gelatin-methacryloy (GelMA) as the matrix, and therapeutic drugs (L-DOPA) were stored in the mesopore of the upconversion micron-rods (UCMRs), dispersing in the GelMA. The molecular motor, as a poreblocker and gate switch, isomerizes under the excitation of ultraviolet and visible light from UCMRs for controlling drug release. This kind of MNP penetrates the epidermis in a painless, non-invasive, and non-infectious way. Under the exposure of NIR light, the L-DOPA in the MNs will be released as needed, and then it seeps into the blood and brain for relieving the symptoms of PD. In the treatment of Parkinson's mice model, this regimen significantly restored motor function, and further mechanistic studies revealed that it reduced neuroinflammation and dopaminergic neuronal death in the substantia nigra. Besides, the released L-DOPA directly entered the blood, which reduces the side effects on the gastrointestinal tract and improves the utilization rate of the drug. These attractive superiorities indicated that the MNP with controlled drug delivery system may be candidate strategies for the treatment of PD and can be used in various related biomedical fields.