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.