Implantable Drug Factories: The Future of On-Demand Medication

A human body producing its own medications on demand sounds like science fiction. Instead, researchers such as Northwestern Engineering’s Jonathan Rivnay are working today to make that technology a reality, and soon.

Rivnay and collaborators Paul E. Sheehan and Omid Veiseh wrote about this emerging treatment in the commentary article “Are Implantable, Living Pharmacies Within Reach?” published October 17 in the journal Science.

“Imagine combining synthetic biology (engineering a cell’s DNA to cre­ate new functions or modify existing ones) with bioelectronics (electrical control over physiological function) in ways that facili­tate sensing, actuation, and wireless com­munication to regulate the production of a drug inside a patient,” the team wrote. “This biohybrid con­cept could be revolutionary, substantially reducing manufacturing costs and conse­quently improving patient access and ad­herence to treatments and, ultimately, health outcomes.” 

Rivnay is a professor of biomedical engineering and of materials science and engineering at the McCormick School of Engineering. His research group engineers organic (polymeric) and biohybrid bioelectronic materials, devices, and systems for interfacing between the complex world of biology and traditional optoelectronics. Over the past five years, Rivnay and collaborators have been working on these concepts, with funding from the Defense Advanced Research Projects Agency, ARPA-H, and the Juvenile Diabetes Research Foundation.

Sheehan is program manager, resilient systems at ARPA-H; and Veiseh is a professor of bioengineering at Rice University.

Below are three key takeaways from the team’s paper.

Biologic drugs are helpful, but can be improved upon

Biologic drugs – treatments sourced from living organisms – have been beneficial to patients since the turn of the century. According to the commentary, around 330 biologic drugs have been approved by the US Food and Drug Administration, including treatments for autoimmune diseases, cancer, and many others. The drugs’ global market size is estimated to be $510 million and projected to jump to $1.3 trillion by 2033.

That does not mean, however, that these drugs are perfected.

Biologic drug treatments are expensive because of production costs, including stabilization, purification, packaging, and marketing. Their efficacy also declines as a patient’s immune system reacts to modified biologics or changes with illness, raising the long-term costs for a patient as diseases need management. Cell-based therapeutics have been developed to address many of these concerns, where engineered cells serve a drug-producing factories in the body. Such approaches would delivery continuous therapies so long as cells were viable in the body. Although some treatments can be implemented continuously without dosing control, many therapies do require regulation.

Bioelectronics could be a solution, Rivnay and his colleagues wrote, because they could flexibly implement control algorithms for either actuation or simulation. Miniaturized electronics have been adapted for wearable and implantable settings to work with the heart, ears, and even the brain. Current systems even implement electronic control of drug pumps using commercial continuous glucose monitors to manage Type I diabetes.

However, the ability to have real-time glycemic control for diabetes patients – without devices attached to their bodies – would be groundbreaking.

“The next frontier in biohybrid systems is to refine and better integrate cell and electronic systems so that production of a biologic in vivo can last long term and can occur on demand,” the authors wrote. “Here, a central goal is developing gene circuits that turn on or off drug synthesis when the engineered cells are activated by an electrical, optical, or even mechanical stimulus.”

A key goal: support cells

Bioelectronics could support implanted cells by providing wireless power transfer and communication, which could enable cell implants to operate freely and communicate with doctors or patients.

“Biohybrid bioelectronic systems are necessarily complex, requiring a clear view of integrating engineered cells, biomaterials, and electronics. Improvements in cell engineering include identifying safe and effective cell lines as chassis for biologics production, and optimizing these cells and their target in vivo environments to ensure cell survival after transplantation,” the authors wrote. “Smaller implants are only possible with more potent cells (cells with high biologic production capacity), which might be accomplished by emerging epigenome editing tools.

“These tools enable precise genetic engineering at specific locations within the cell’s genome and can tune cellular phenotypes such as potency and resilience against cell death. Gene circuits capable of logic could complement bioelectronic circuits.”

One example from the authors was that secretion of biologics from cells could be regulated in response to physiological states, done by sensing disease biomarkers. This could apply to a series of illnesses, including cancer, diabetes, and autoimmune diseases. 

Advances should be intentional and well-planned

Innovations can only maximize their impact if they are cost-effective and durable. Bioelectronics operate in harsh conditions surrounded by biofluids and other body chemicals and structures.

“Stable biochemical sensors that monitor biologics or native cytokines and hormones are a particular challenge, requiring isolation of the elec­tronics (encapsulation) but also exposure of the sensor probe to biofluids,” the authors wrote. “As these advances come to fruition, they will need to integrate with ongoing improvements in communication, power efficiency, power transfer, and power storage that support miniaturized devices that can be deployed in a minimally invasive manner.

“Implantable biologic factories may rev­olutionize health care, but they require manufacturing processes that scale up pro­duction at low cost.”

Rivnay and his colleagues recommend consideration of how advanced biohybrids would fit into society. Today, gene therapies promise lifelong cures but are costly, limiting their prevalence in the market. The authors suggest something of a subscription model, where the overall cost could be divided by monthly or yearly payments that would assure the upkeep and maintenance of the biohybrid system.

“With any disruptive technology, the ad­vantages come with key questions of trust and adoption, with added concerns over security and privacy arising from the use of bioelectronic control and communica­tion. However, overcoming these techni­cal and nontechnical hurdles, along with the superior benefits and payment models, will catalyze new approaches to equitable and accessible health care for all.”