Electrochemical evaluation of a nanofluidic membrane for drug delivery

Chronic conditions such as rheumatoid arthritis, diabetes, and hypertension affect 80% of US population over 65 years of age, accounting for 66% of all deaths and 75% of healthcare expenditures. The high healthcare cost is mostly due to the focus on acute episodic care rather than continuous management. Moreover patient difficulty in adherence to strict dosing schedules threatens therapy efficacy. Conventional delivery approaches such as oral or parenteral, usually lead to a peak in plasma drug concentration that could reach toxic levels. This peak is usually followed by an exponential decrease in concentration which results in a short efficacy window. On the other hand, a constant and sustained release at the therapeutic concentration level, has been shown to increase treatment efficacy. Several technologies have been developed to achieve a zero-order release kinetics, among them, the one we focused our attention on is concentration driven diffusion through a nanofluidic membrane. Even if a constant release profile results in reduced toxicity and increased efficacy with respect to conventional administration methods, this approach is not the best available strategy for every pathologies. In fact, previous studies have shown that drug administration in sync with the circadian or other rhythmic body cycles increase therapeutic efficacy for pathologies such as hypertension and rheumatoid arthritis. This therapeutic administration regime is known as chronotherapy. While commercially available implants allow for sustained release, the development of devices for tunable release is still challenging. The only one currently on market is based on a peristaltic pump which is prone to mechanical failure in time. Here we propose an implantable device for tunable remote drug delivery that is based on nanofluidic membrane with the goal of low power consumption, Bluetooth controlled implant for time dependent drug administration The aim of this thesis is to study how the application of an external electric field on a nanofluidic membrane can modify its drug release profile. The electric field, key feature of this device, has been applied between an electrode buried in the membrane and a reference one in solution. The efficacy of applied electric field on modulation of drug release depends on several factors, such as material properties, morphology of the structure , size of nanochannels, and used drug. This work compares different membrane structures in terms of efficacy of modulation, through electrochemical measurements and in vitro studies. A proper tuning of membrane fabrication parameters led to repeatable modulation of drug in in vitro studies, with the application of a low applied voltage. Overall this study gave a proof of concept of drug modulation leveraging a nanofluidic membrane. The integration of this technology with an implantable device the can be remotely controlled, can allow for personalized therapy management resulting in an overall better quality of life.