Getting drugs to pass through the mucus barrier is a major pharmacokinetic challenge as is, and it is an especially daunting task for the development of nano-based therapeutic agents. Ever since nanoparticles have been looked into as possible ferrying vehicles to overcome the mucus barrier problem, each either had trouble moving through the mucus or was not degradable so as to release their pharmacological cargo at the therapeutic site. Now Johns Hopkins University researchers created a biodegradable particle that can move through mucus and be preprogrammed to open in a time frame lasting from days to weeks.
The new biodegradable particles comprise two parts made of molecules routinely used in existing medications. 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.
In Hanes’ previous studies with mucus-penetrating particles, latex particles could be effectively coated with PEG but could not release drugs or biodegrade. Unlike latex, however, PSA can degrade into naturally-occurring molecules that are broken down and flushed away by the body through the kidney, for example. 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.
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.”
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. In a related research report, the group showed that the particles can efficiently encapsulate several chemotherapeutics, and that a single dose of drug-loaded particles was able to limit tumor growth in a mouse model of lung cancer for up to 20 days.
Images:This image shows the biodegradable nanoparticles produced by the Justin Hanes Lab at Johns Hopkins University as seen under a scanning electron microscope. Top: This biodegradable nanoparticle developed by the Justin Hanes Lab at Johns Hopkins University is shown here at microscale for easier viewing. The particle displays its polymer coating as a red fluorescent glow. Hanes’ biodegradable nanoparticles have the ability to penetrate mucus barriers in the body to deliver drugs. Bottom:
Press release: Biodegradable Nanoparticles Can Bypass Mucus Barrier and Release Drugs Over Time…
Abstract in PNAS: Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier