In the race to design therapeutic bullets for diseases such as cancers, bacterial infections and obesity, drug researchers are paying ever-closer attention to the mechanisms that fire them. Their effectiveness is improved significantly, for example, when they can be safeguarded from the stomach’s acidic environment and delivered directly to the site of an infection for controlled release.
But a primary hurdle is making sure they are released into the bloodstream at all.
“The challenge of modern pharmaceuticals is that they’re often not water soluble,” says Rajesh Davé, distinguished professor of chemical, biological and pharmaceutical engineering. “Newly discovered molecules with the desired mechanisms tend to be larger and have higher hydrophobicity. And since blood is largely composed of water, such drugs do not get absorbed and so cannot reach their targets. Our task is to make them soluble enough to be available in the blood stream.”
Davé, who specializes in particle engineering, has spent the last several years grinding drugs into ever-tinier bits to enhance solubility and then coating each one with nanoparticles to prevent them from being degraded before they reach their targets and to optimize their flow. The coating adheres to the drug particles, which may be as small as 50 microns, after they are shaken together at a 100 g-force.
In a recent project funded by the U.S. Food and Drug Administration, Davé has been asked to come up with another delivery platform, which involves spreading soluble nanoparticles of medications uniformly across a thin film. While it would benefit people who are unable to swallow, such as Alzheimer’s patients, this platform is also thought to be a highly efficient way to deliver drugs because it keeps them from agglomerating. Clumping negates the advantage of nanoparticles, he notes, since the clumps behave as very large particles with a lower available surface area for adsorption. A significant amount ends up being excreted.
“Particle engineering allows for the proper dispersion of nanoparticles and therefore a higher utilization rate. This also means we can use a smaller amount of medication,” Davé says. “And we don’t need to use liquids or solvents or any other added ingredient to deliver these drugs, which, among other benefits, allows us to eliminate the pharmaceutical residue that is normally excreted as waste, contaminating the water supply.”
He adds, “We’re trying to push the limits of how much we can put on a tiny film so that they become useful for a larger variety of therapeutics, such as pain relief, while achieving a predictable performance.”
Davé is currently the site-leader and one of the founders for the National Science Foundation (NSF)-funded Engineering Research Center on Structured Organic Particulate Systems, which focuses on manufacturing processes for the pharmaceutical industry. Collaborators include NJIT, Rutgers University, Purdue University and the University of Puerto Rico at Mayaguez. Last year, Davé received his ninth patent for coming up with a manufacturing process for coating fine particles less than the diameter of a human hair that does not require water, organic solvents or heat.
In 2015, Davé won a major career award from the American Institute of Chemical Engineers, the organization’s Lectureship Award in Fluidization, for a process for agitating solids such as powders and particles in order to make them behave like liquids. By fluidizing particles, engineers are able to adapt their structure and behavior to improve products ranging from cement, to cookies, to fuel, to cancer medications, to sunscreen, while making it faster and more efficient to manufacture them.
Among other processing improvements, he has developed methods to mask the bitter tastes of drugs to make them more palatable for children as well as for adult patients who have difficulty swallowing.
His colleague, Xiaoyang Xu, an assistant professor of chemical engineering, designs therapeutic mechanisms that navigate the body by mimicking its environment, thus eluding the immune system’s sometimes over-attentive sentinels, stopping at a precise location for a specified period, and then biodegrading. Xu’s focus is nanomedicines, high-concentration therapies delivered in millions of tiny packets that coat their target. Antibiotics are a good example of this approach, he notes. Effectively delivered, an anti-infection agent should kill the disease before it has time to develop resistance.