As a scientist, engineer, and serial inventor, my work focuses on developing new biologically focused tools which allow for previously impossible interactions with the body. Some of this work has resulted in the invention of orally dosed capsules which may be able to replace painful and cumbersome injections. Using clever engineering designs, my devices are able to autonomously orient, localize, and deploy cargo inside of the gastrointestinal tract, enabling the systemic absorption of insulin and other biologic molecules which are traditionally degraded by enzymes in the stomach and small intestine. As demonstrated through cost effectiveness analyses, this work could have a profound impact on the healthcare system.
Looking towards the future, I hope to be able to develop therapeutic pills and implants that combine conformable and degradable electronics with novel drug delivery systems. These devices could usher in a new era of smart medications which physically, electrically, and chemically interact with the body.
Ingestible Robotic Capsules
Ingestible Self-Orienting Pills for Oral Biologic Drug Delivery
Biomacromolecules transformed our capacity to effectively treat diseases; however, their rapid degradation and poor absorption in the gastrointestinal (GI) tract generally limit their administration to parenteral routes. An oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise’s ability to passively reorient, we developed an ingestible self-orienting millimeter-scale applicator (SOMA) that autonomously positions itself to engage with GI tissue. It then deploys active pharmaceutical ingredients directly into the vascularized layers of stomach tissue while avoiding perforation. We conducted in vivo studies in rats and swine that support the applicator’s safety and, using insulin, mRNA, adalimumab, and GLP-1 Receptor agonists as model drugs, demonstrated that the SOMA delivers plasma levels comparable to those achieved with subcutaneous administration. The technology described in this work has been exclusively licensed to Novo Nordisk to bring into clinical trials. (Abramson et al, Science, 2019) (Abramson et al, Nature Biotechnology, 2021) (Abramson et al, Matter, 2022)
Luminal Unfolding Microneedle Injector Capsules
We developed an ingestible capsule, termed the luminal unfolding microneedle injector, which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies, the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug, we showed that, when actuated, the luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake >10% of that of a subcutaneous injection over a 4-h sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of biologic drugs. (Abramson, Caffarel et al, Nature Medicine, 2019)
Ingestible electronic devices enable noninvasive evaluation and diagnosis of pathologies in the gastrointestinal (GI) tract but generally cannot therapeutically interact with the tissue wall. We developed an orally administered electrical stimulation device characterized in ex vivo human tissue and in in vivo swine models, which transiently anchored itself to the stomach by autonomously inserting electrically conductive, hooked probes. The probes provided stimulation to the tissue via timed electrical pulses that could be used as a treatment for gastric motility disorders. To demonstrate interaction with stomach muscle tissue, we used the electrical stimulation to induce acute muscular contractions. Pulses conductively signaled the probes’ successful anchoring and detachment events to a parenterally placed device. The ability to anchor into and electrically interact with targeted GI tissues controlled by the enteric nervous system introduces opportunities to treat a multitude of associated pathologies. (Abramson et al, Science Advances, 2020)
Sensors for Real-Time Tumor Regression Monitoring
Quantifying Quality of Life
Cost Effectiveness Analysis demonstrates the value of a capsule over an injection
Novo Nordisk’s oral semaglutide, which has undergone multiple phase 3 clinical trials, represents the first oral biologic medication for type 2 diabetes in the form of a daily capsule. It provides similar efficacy compared with its weekly injection counterpart, but it demands a dose on the order of 100 times as high and requires more frequent administration. We perform a cost effectiveness analysis using a first and second order Monte Carlo simulation to estimate quality-adjusted life expectancies associated with an oral daily capsule, oral weekly capsule, daily injection, and weekly injection of semaglutide. We conclude that the additional costs incurred to produce extra semaglutide for the oral formulation are cost effective, given the greater quality of life experienced when taking a capsule over a weekly injection. We also demonstrate that the potency of semaglutide allows the formulation to be cost effective, and less potent drugs will require increased oral bioavailability to make a cost effective oral formulation using the same technology. The MIT-developed ingestible injection systems described above, however, provides a greater bioavailability compared to the oral semaglutide capsule and could cost-effectively enable the oral delivery of a variety of less potent biomacromolecules, including: monoclonal antibodies; nucleic acids; and peptides. (Abramson et al, J Pharm Sci, 2019.)