(28af) On-Demand Electrochemically Controlled Fluorescein Release from an Ultrasonically Powered Implant

On-demand drug delivery systems that control the release of drug molecules are promising for a wide range of therapeutic applications. When combined with wireless implants for controlled drug delivery, they can reduce overall dosage and side effects. However, electronically controlled release implants are often nondegradable over time, use toxic components, and are nonapplicable to a wide scope of potential drugs, which discourages their use in implantable applications. Combining an ultra-low voltage ultrasound power and responsive nanoparticles, have demonstrated exceptionally high drug loading capacity and more drug release per stimulus due to their higher surface-to-volume ratios and tunable pore sizes. This may overcome the limitations of drug loading and release capacity and an efficient mechanism to wirelessly transfer power due to its low propagation loss, high safety limit, and focusing capabilities meaning that implants can be placed deeply near the target area. We approach these limitations by understanding the counterion exchange mechanism with ions in the surrounding solution, which can be significant in vivo. To minimize passive ion exchange at the surface, we incorporated a silicone oil-PDMS gel coating over the nanoparticulate film. We hypothesize that the oil-PDMS coated layer would result in maximize drug loading while minimizing passive release. We test this hypothesis using a novel on-demand release system for negatively charged compounds, FL-loaded polypyrrole nanoparticulates (PPy NPs). We prepare a fluorescein (FL) leak experiment from the silicone oil-PDMS coated samples in Ringer's solution out to 24 hours. At the end of the 24 h experiment, the FL release was electrically triggered using a potentiostat to demonstrate that the drug delivery module (DDM) was still functional. The release system is based on a modified electroresponsive PPy NP film designed to minimize ion exchange with the stored compound - a major passive leakage mechanism. We further designed an ultrasonically powered mm-sized implant to electronically control the on-demand drug delivery system in vivo. Release kinetics are characterized both in vitro and in vivo in mice using FL as a model drug, demonstrating the feasibility of wireless, controllable drug release using an ultrasonically powered implant. The synthesis NPs and an ultrasonically powered implant developed here can be extended to a to a wide scope of potential drugs for studying the release of macromolecules (e.g., polypeptides and nucleic acids) and negatively charged drugs with intrinsic weak electric potentials.