Refillable Silicone Pump with Precise Switching for Timed Therapeutic Delivery

Naaz Thotathil¹John J. Amante¹Micah Wingell¹Keegan Mendez²Ellen T Roche²Cathal Kearney^1*

• ¹University of Massachusetts Amherst, Amherst, United States
• ²Massachusetts Institute of Technology, Cambridge, United States

Given the precise temporal coordination of natural biological processes, administering therapeutic agents at specific times can be used to enhance efficacy in a range of applications. To achieve such controlled drug delivery, various stimulus-responsive techniques (e.g., ultrasound, temperature changes, and electromagnetic radiation) have been developed. However, many of these current methods exhibit limitations, such as premature leakage prior to stimulus activation or delayed and prolonged responsiveness to stimuli. Our research introduces a soft robotic pressure-actuated drug delivery pump aimed at improving therapeutic efficacy through precisely-timed drug administration. This device utilizes silicone – a low-modulus material – for both the therapeutic reservoir and the actuation chamber to create a biocompatible and conformable interface, facilitating controlled drug release and offering the potential to be adapted as an implantable drug delivery system. Importantly, the system features a reliable On/Off mechanism – confirmed by actuating to ~80% of opening pressure over 5 days – which addresses a key limitation in many existing technologies. In vitro, the device was used to deliver a range of therapeutics and had non-significant differences versus manual delivery of therapeutics: antibiotics (doxycycline; reduced E. coli viability by 49.6 % vs. 49.8 %); adeno-associated virus (AAV; transduced 73.5 % vs. 76.2% of cells); dexamethasone (2D fibroblast scratch wound closure 50.9 % vs. 51.0 %); and successful delivery of viable cells (viability of 83 % vs. 100 %). We additionally developed a finite element model to model the pressure/volume release trend, and demonstrated the effect of membrane stiffness on release. Our results demonstrate that the device can consistently administer therapeutics and molecules of various sizes and functions while maintaining their bioactivity, showcasing its potential for repeated, precisely-timed therapeutic delivery.