Researchers at the Johns Hopkins University have created biodegradable nanosized particles that can easily slip through the body’s sticky and viscous mucus secretions to deliver a sustained-release medication cargo. The mucus-penetrating biodegradable nanoparticles were developed by an interdisciplinary team led by Justin Hanes, a professor of chemical and biomolecular engineering in the Whiting School of Engineering at Johns Hopkins. The team’s work was reported recently in the Proceedings of the National Academy of Sciences. Hanes’ collaborators included cystic fibrosis expert Pamela Zeitlin, a professor of pediatrics at the Johns Hopkins School of Medicine and director of pediatric pulmonary medicine at the Johns Hopkins Children’s Center.
“Cystic fibrosis mucus is notoriously thick and sticky and represents a huge barrier to aerosolized drug delivery,” she said. “In our study, the nanoparticles were engineered to travel through cystic fibrosis mucus at a much greater velocity than ever before, thereby improving drug delivery. This work is critically important to moving forward with the next generation of small molecule and gene-based therapies.” Also these nanoparticles, which degrade over time into harmless components, could one day carry life-saving drugs to patients suffering from dozens of health conditions, including diseases of the eye, lung, gut or female reproductive tract.
Beyond the potential applications for cystic fibrosis patients, the nanoparticles also could be used to help treat disorders such as lung and cervical cancer, and inflammation of the sinuses, eyes, lungs and gastrointestinal tract, said Benjamin C. Tang, lead author of the recent journal article and a postdoctoral fellow in the Department of Chemical and Biomolecular Engineering. “Chemotherapy is typically given to the whole body and has many undesired side effects,” he said. “If drugs are encapsulated in these nanoparticles and inhaled directly into the lungs of lung cancer patients, drugs may reach lung tumors more effectively, and improved outcomes may be achieved, especially for patients diagnosed with early stage non–small cell lung cancer.”In the lungs, eyes, gastrointestinal tract and other areas, the human body produces layers of mucus to protect sensitive tissue. But an undesirable side effect is that these mucus barriers can also keep helpful medications away.
“The major advance here is that we were able make biodegradable nanoparticles that can rapidly penetrate thick and sticky mucus secretions, and that these particles can transport a wide range of therapeutic molecules, from small molecules such as chemotherapeutics and steroids to macromolecules such as proteins and nucleic acids,” Hanes said. The new biodegradable particles comprise two parts made of molecules. An inner core, composed largely of polysebacic acid (PSA), traps therapeutic agents inside. A particularly dense outer coating of polyethylene glycol (PEG) molecules, which are linked to PSA, allows a particle to move through mucus nearly as easily as if it were moving through water and also permits the drug to remain in contact with affected tissues for an extended period of time.
PSA can degrade into naturally occurring molecules that are broken down and flushed away by the body through the kidney. As the particles break down, the drugs loaded inside are released. This property of PSA enables the sustained release of drugs, said Samuel Lai, assistant research professor in the Department of Chemical and Biomolecular Engineering, while designing them for mucus penetration allows them to more readily reach inaccessible tissues. Polyethylene glycol acts as a shield to protect the particles from interacting with proteins in mucus that would cause them to be cleared before releasing their contents. Jie Fu, an assistant research professor, also from the Department of Chemical and Biomolecular Engineering, said, “As it degrades, the PSA comes off along with the drug over a controlled amount of time that can reach days to weeks.”