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.
Pre-clinical research and evaluation of drugs and therapeutic regimens play a key role in the development of new medical interventions. However, this process is challenged by the complexity in determining appropriate dosing, administration strategy, and treatment duration for each research model. To address these challenges, we propose to develop an innovative remotely controlled nanofluidic implant for tunable drug delivery. This versatile and broadly applicable platform represents an enabling technology that can significantly impact the pre-clinical development of drugs and therapeutic strategies.
