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How mucus affects drug delivery and medical research

Rebecca Carrier speaks into a microphone at a podium during a symposium.
Professor Rebecca Carrier of Northeastern University studies how mucus affects drug delivery. Photo by Alyssa Stone/Northeastern University

Mucus is a thick, sticky substance that lines many parts of the body and plays an important role in protecting and lubricating vital tissues.

Mucus also plays an important role in drug development.

This topic is one of the main areas of interest of Rebecca Carrier, a professor of chemical engineering at Northeastern University and director of the university's Advanced Drug Delivery Research Lab.

“Why is mucus so interesting?” Carrier recently asked an audience at the Curry Student Center on the Boston campus. “It lines all of our moist epithelial surfaces. It really forms the first barrier between us and the outside world.”

Carrier was one of over a dozen leading biomaterials experts who spoke during the Society for Biomaterials' recent Northeast Symposium 2024.

The two-day conference, hosted by Northeastern, brought together industry experts to discuss the field of biomaterials – from immunoengineering and regenerative medicine to bioelectrical materials and biointerfaces.

Mucus is a natural biological substance that plays an important role in smell, reproduction and healthy gut flora. But it also plays an important role in the absorption of medications in the body, says Carrier.

At the macro level, a mucous membrane lining has a thin, shiny appearance. At the microscopic level, it appears like “one continuous layer of material.”

“If you zoom in and look down at this continuous blanket of material, you get an idea of ​​this nanoporous network,” she says.

Rehecca Carrier speaks at a symposium.
09/20/24 – BOSTON MA. – Professor Rebecca Carrier of Northeastern University speaks at the 2024 SFB Northeast Symposium hosted by Northeastern University on Friday, September 20, 2024 in the Curry Student Center. Photo by Alyssa Stone/Northeastern University
Rebecca Carrier speaks to a class at a symposium.
09/20/24 – BOSTON MA. – Professor Rebecca Carrier of Northeastern University speaks at the 2024 SFB Northeast Symposium hosted by Northeastern University on Friday, September 20, 2024 in the Curry Student Center. Photo by Alyssa Stone/Northeastern University
Students listen to Rebecca Carrier at a symposium.
A student puts his hand on his neck while taking notes at a symposium.
09/20/24 – BOSTON MA. – Professor Rebecca Carrier of Northeastern University speaks at the 2024 SFB Northeast Symposium hosted by Northeastern University on Friday, September 20, 2024 in the Curry Student Center. Photo by Alyssa Stone/Northeastern University
Professor Rebecca Carrier heads the university's Advanced Drug Delivery Research Lab. Photo: Alyssa Stone/Northeastern University

To understand how to navigate this network, Carrier says it is important not only to know its physical properties but also its chemical nature.

Mucus is mainly composed of molecules called mucins, which communicate and bond together in various ways, including disulfide bonds, hydrogen bonds, hydrophobic interactions, and electrostatic interactions.

“The same types of interactions that occur between mucin molecules may also be important in controlling things that are trying to be transported through the mucus dough, such as drug delivery systems and drugs,” she says.

To study these interactions, Carrier and other researchers in their lab use a technique called multiple particle tracking.

The researchers collect intestinal mucus, place it under a microscope and add fluorescent substances, often nanoparticles, sometimes bacteria, and track their movement through the mucosal gel using video microscopy.

“We then use an image analysis algorithm to track these particles so that we can analyze their trajectories and extract quantitative parameters that reflect the transport of the particles in the gel and the barrier properties of the gel,” she says.

Carrier first became interested in mucus when she was working as a scientist at Pfizer. While working on drug formulation development, she recalls a smaller company approaching Pfizer about penetrating the intestinal wall by “liquefying the mucus barrier.”

“I found that fascinating because if you look at the pharmaceutical literature, the mucus barrier isn't traditionally discussed as a significant barrier,” says Carrier. “It's often referred to as an undisturbed water layer, just a passive diffusion barrier that things have to pass through.”

Researchers at Pfizer therefore conducted experiments to test this theory and understand how these drugs interact within the barrier. They concluded that the barrier significantly hinders their passage.

Recently, researchers at Northeastern University's Advanced Drug Delivery Research Lab teamed up with AbbVie Pharmaceuticals to understand how mucosal barriers might impact their drugs.

“A lot of my work now focuses on problems I've encountered in industry,” she says. “So we're doing a lot of work on drug delivery, but we're not developing new systems, we're trying to understand mechanistically the transport processes in the gut and how they're affected by different delivery systems.”

Carrier's research in her “gut lab” focuses on studying the effects of various external factors on mucus. For example, lipids, compounds found in many foods and medications, can significantly affect the barrier properties of mucus.

“We were very interested in understanding how we could develop better model systems to study the mucosal barrier and, in a more physiological context, ask some of these questions about the mucosal barrier and how it changes when it comes into contact with different systems and what ability different systems have to penetrate it.”

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