Automated Refilling Systems for Subcutaneous Nanofluidic Implantable Drug Delivery Devices

Long-acting (LA) implantable drug delivery systems (IDDS) present an effective strategy for managing or preventing chronic conditions through sustained parenteral therapeutic administration, thereby enhancing treatment adherence by minimizing dosing frequency. Currently available drug-releasing implantable devices in the market necessitate surgery for removal and replacement. The ability to refill these implantable devices extends their lifespan and treatment duration. Addressing this concern, Dr. Alessandro Grattoni's laboratory at the Houston Methodist Research Institute has developed a transcutaneously refillable implant (nDS) capable of reloading with solid particles. This implant demonstrates a 1000-fold increase in drug load efficiency compared to implants loaded with saturated liquid solutions. This thesis aims to design and realize a device for drug refilling without the need for cumbersome external pumps. Two alternative approaches were explored to achieve this goal. The first approach focused on designing a device that is easy to produce, use, and cost-effective, considering the potential deployment of nDS for HIV Pre-exposure prophylaxis (PrEP) in resource-constrained regions. This device employs mechanical and hydraulic principles in its working mechanism. The second approach aimed at designing a high-performance device for use in countries with a higher healthcare budget. However, it was eventually adapted into a laboratory tabletop equipment for conducting tests and analyzing suspension and solution properties in a controlled environment. Extensive in vitro and in vivo experiments, utilizing a rat model, were conducted to evaluate the efficacy of both devices, and both demonstrated promising performances aligned with their expected behaviors. In conclusion, this research contributes to the practical deployment of a critical healthcare device, nDS, with potential applications in diverse settings.