Working to Improve Oral Drug Delivery

Generations of women have contributed to engineering, and Clark School women are proud to be part of that tradition. In honor of women’s history month, the Clark School is celebrating one female engineering faculty member each day. Read about today’s featured faculty member, Silvia Muro.

For decades, scientists have worked to target therapeutics to specific markers within the body in efforts to improve delivery of medication to the target site while avoiding interaction with healthy tissue. But, the corrosive environment of the gastrointestinal (GI) tract has long prevented scientists from pursuing methods of oral drug delivery that employ what are known as targeted nanocarriers – nanomaterial that is used to transport another substance, such as a therapeutic – to reach certain organs or cells while steering clear of others.

Recognizing this challenge, Fischell Department of Bioengineering (BIOE) Associate Professor Silvia Muro (Joint, Institute for Bioscience and Biotechnology Research(link is external), IBBR) and a team of University of Maryland researchers are exploring new drug delivery strategies that could be used to deliver therapeutics to targets in the GI tract, as well as targets inside GI cells or across the GI tract for circulation in the bloodstream.

Scientists have long used targeted nanocarriers in intravenous therapy treatments. Put simply, a targeted nanocarrier features a biological molecule that serves as a targeting molecule that is “programmed” to recognize a marker. As such, scientists are able to deliver therapeutics to site-specific targets without causing harm to healthy organs or cells. This specificity is crucial: in chemotherapy treatment, for example, the use of targeted nanocarriers allows doctors to attack tumor cells while minimizing the risk of chemotherapy’s toxicity to healthy cells in the body.

But, when scientists explore treatment options for diseases of the gut – such as Crohn’s disease or a variety of inflammatory diseases – they face limitations. In part, this is because doctors aiming to target nanocarriers to sites in or across the GI tract have been limited to using IV therapies.

“Typically, drug delivery technologies involve fabrication of a nanocarrier that bears a pharmaceutical drug of interest,” Muro explained, “The nanocarrier is then coated with a biological molecule, which serves as a targeting entity. This targeting coating is designed to recognize a specific marker in the body, bringing the drug to the site of disease; however, in oral delivery, the biological coating gets degraded in the stomach and the targeting property of the drug nanocarrier is lost. This is why scientists have not focused on targeting strategies for oral delivery.”

But, Muro and her team are hopeful they have found a solution.

She and her fellow researchers have placed targeted nanocarriers into microcapsules, specially designed to survive the harsh environment of the stomach.

“This is a technique classically used to deliver therapeutics orally, to protect drugs from premature inactivation while in route to the intestines,” Muro said. “But, it has never been used before to protect targeted nanocarriers.”

To illustrate this new concept the team used microcapsules made of a chitosan shell and alginate core. Chitosan is a biological compound found in the shells of crustaceans, and alginate is a naturally occurring polysaccharide obtained from various species of seaweed.

Once these microcapsules bypass the stomach, they disintegrate in the intestines, thereby liberating the targeted nanocarriers there and allowing them to bind to specific disease markers.

“This approach enables the use of targeted nanocarriers for oral delivery,” Muro said. “This opens an opportunity to investigate whether targeting drugs to specific intestinal markers improves intestinal delivery of therapeutics and their uptake into the circulation.”

Because drug nanocarriers provide control over the stability and release of therapeutics, and targeting provides a means to specifically direct a drug toward disease sites, combining these properties with oral delivery – a patient-friendly route – may signify a great improvement in scientists’ ability to deliver disease-treating drugs in an efficient and safe manner, Muro said.

For Muro and her research team, improving drug delivery techniques is a life’s passion. After all, the next major breakthrough in the treatment of cancers, Alzheimer’s disease, or even genetic conditions relies in part on scientists’ collective ability to deliver therapies to affected sites of the body while minimizing harm to healthy cells

Published April 1, 2017