A nanofluidic platform for tunable drug delivery

每一种新的药物或治疗方案，无论是基于生物制剂还是化学制剂，都需要 为评估剂量、配方、给药时间表和 持续时间。然而，这些研究是复杂、昂贵和耗时的，表明需要一种 多功能且有效的支持工具，可实时测试和纠正不适当的剂量、持续时间、 和给药频率。在这项研究中，我们将开发一种远程控制植入物 纳米流体技术，能够精确地增加、减少、激活或中断药物 体内给药。该技术具有很高的创新性，可提供长期、精细、连续的调制 在剂量集中使用嵌入式栅极和蓝牙低能无线电 频率(RF)通信。进一步的区别基于三个关键方面：1)静电 纳米通道的门控，2)超低功耗，以及3)植入物的多功能性 药物成分(小分子、蛋白质和纳米颗粒都可以释放)，动物大小( 植入物适用于小型和大型动物)、材料组成(廉价部件)。 为了研制该装置，我们提出了以下实验目标：1)设计和装配 远程控制的植入物。具有栅电极的纳米沟道膜和 包含药物储存器、电子设备、电池和远程控制系统的植入式装置 将生成一个原型来控制、增强、减少、中断和重新激活 探员们。目的2)研究药物的体外可调控性释放。在这里，我们 将展示植入物的功能及其在生物医学研究中的广泛适用性 不同分子大小和物化性质的药物。目的3)测试射频控制的 用于在小动物和大动物体内可调给药的植入物。设备将被皮下注射 在啮齿类动物(小型植入物)和猕猴(大型植入物)中进行了测试。药物输送的远程调制 将通过代表性药物的药代动力学分析进行评估。的完整性和表现 同时还将研究射频通信。如果成功，拟议的调查将 创造一种广泛适用的工作技术，利用纳米通道膜精细地 控制调节广谱药物的治疗性释放以解决生物医学问题 跨多个系统或疾病的研究需求。

Every novel drug or therapeutic regimen, whether based on biological or chemical agents, requires extensive investigations for the assessment of dosing, formulation, administration schedule, and duration. These studies, however, are complex, costly and time consuming, indicating the need for a versatile and effective enabling tools to test and correct in real time for inappropriate dosing, duration, and frequency of administration. In this study, we will develop a remotely controlled implantable nanofluidic technology that enables precise increase, decrease, activation, or interruption of drug delivery in vivo. The technology is highly innovative, and offers long-term, fine, continuous modulation in dose centered on the use of embedded gate electrodes and Bluetooth Low Energy Radio Frequency (RF) communication. Further distinction is based on three key aspects: 1) electrostatic gating of nanochannels, 2) ultra-low power consumption, and 3) implant versatility with respect to drug composition (small molecules, proteins and nanoparticles can all be released), animal size (the implant is suitable for small and large animals), and material composition (inexpensive components). To develop this device, we propose the following experimental aims: Aim 1) To design and assemble remotely controlled delivery implants. A nanochannel membrane with gate electrodes and an implantable device containing a drug reservoir, electronics, a battery, and a remote control system will generate a prototype to control, enhance, decrease, interrupt, and reactivate the release of agents. Aim 2) To investigate the tunable and remote controlled release of drugs in vitro. Here, we will demonstrate function of the implant and its broad applicability to biomedical studies involving drugs of different molecular size and physicochemical properties. Aim 3) To test the RF-controlled implant for the tunable delivery of drugs in small and large animals. Devices will be subcutaneously tested in rodents (small implant) and macaques (large implant). Remote modulation of drug delivery will be assessed via pharmacokinetic analysis of a representative drug. Integrity and performances of RF-communications will be simultaneously studied. If successful, the proposed investigation would create a broadly applicable working technology that leverages nanochannel membranes for finely controlled modulation of therapeutic release of a broad spectrum of agents to address biomedical research needs across multiple systems or diseases.