Tiny device with engineered cells acts as internal drug factory

· News-Medical

A multi-institutional team of scientists, co-led by Northwestern University, has taken a crucial step toward implantable "living pharmacies" - tiny devices containing engineered cells that continuously produce medicines inside the body.

In a new study, the team engineered cells to simultaneously produce three different biologics - an anti-HIV antibody, a GLP-1-like peptide used to treat type 2 diabetes and leptin, a hormone that regulates appetite and metabolism. When implanted under the skin of a small animal model, the device kept drug-producing cells alive and stably delivered all three therapies at once.

Called HOBIT (short for hybrid oxygenation bioelectronics system for implanted therapy), the new system integrates the engineered cells with oxygen-producing bioelectronics. Roughly the size of a folded stick of gum, the design shields cells from the body's immune system while also providing cells with oxygen and nutrients to keep them alive and producing biologic drugs for several weeks.

With more work, living pharmacies hold the potential to treat chronic conditions with a single, long-lasting therapy - bypassing the need for patients to carry, inject or remember to take medications.

The study will be published on Friday (March 27) in Device, a journal published by Cell Press. The project is jointly led by Northwestern, Rice University and Carnegie Mellon University.

A breath of fresh air

While implantable living pharmacies could transform the treatment of numerous diseases, these tiny cellular factories have faced a stubborn biological barrier: oxygen. When engineered cells are packed together inside an implant, they compete for oxygen to live. Without enough supply, many cells die - limiting how much medicine the implant can produce.

HOBIT contains three primary components: A cell chamber to hold the genetically engineered cells, a miniature oxygen generator, and electronics and a battery to regulate oxygen production and wirelessly communicate with external devices. Because the device produces oxygen directly inside the implant, the cells receive a steady supply - even in low-oxygen environments.

"We are producing oxygen directly where the cells need it," Rivnay said. "That allows us to support much higher cell densities in a much smaller space. Cell densities in HOBIT were roughly six times higher than conventional unoxygenated encapsulation approaches."

Extending the viability of cells

To demonstrate the platform's capabilities, the researchers engineered cells to produce three different biologics, each with a different half-life. The team implanted the devices under the skin of rats and monitored drug levels in the animals' bloodstreams for 30 days.

In animals with the oxygenated implants, blood measurements showed sustained levels of all three biologics throughout the study period. In animals implanted with devices without oxygenation, the biologics with a shorter half-life became undetectable by day seven. And longer half-life molecules declined steadily over time.

At the end of the testing period, roughly 65% of the cells in the oxygenated devices remained viable compared with roughly 20% in control devices.

Next, the research team plans to test the technology in larger animal models and explore disease-specific applications, including therapies based on transplanted pancreatic cells.

"We're beginning to see how bioelectronics and cell therapy can work together in a single platform," Rivnay said. "As these technologies continue to develop, devices like this could eventually act as programmable drug factories inside the body - delivering complex therapies in ways that simply aren't possible today."

Source:

Northwestern University

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