Name: Bob Prud’homme, professor of chemical and biological engineering and director of the program in engineering biology.

Drug and biocompatible polymers are mixed in the small holes. Photo by Frank Wojciechowski.

Invention: Flash NanoPrecipitation, a technique for encapsulating therapeutic and diagnostic molecules in nanoparticles to improve treatment and monitoring of diseases including cancer and tuberculosis.

What it is: This technology embeds drugs and other molecules inside nanometer-size, biocompatible particles. “Our coating technology enables protection of a drug or imaging molecule so it can circulate and travel to disease sites where it is slowly released,” said Prud’homme.

View a video of Flash Nanoprecipitation.

How it works: As the name suggests, Flash NanoPrecipitation’s key ingredient is speed. Prud’homme’s invention involves squirting a small quantity of drug together with a biocompatible polymer into a tiny cavity where fluid flow rapidly mixes the drug and polymer with water. The technique works best with drugs or other molecules that do not dissolve well in water, a quality known as hydrophobicity. Instead, the drug molecules cluster together inside the polymer. Prud’homme’s collaborators have shown that non-hydrophobic drugs can be modified to be sufficiently hydrophobic so that they are able to be packaged into the nanoparticles.

In addition to speed, the success of Prud’homme’s technique rests on the choice of polymer. Instead of a single polymer, Prud’homme uses a “co-polymer” made of linked units of polyethylene glycol (PEG) and polylactide. The hydrophobic polylactide moves toward the interior of the particle along with the drug, while the PEG is hydrophilic (water-loving) so it moves to the exterior of the particle. “Rapid mixing, combined with the right kind of polymers, keeps the particles from growing too large during the aggregating process,” said Prud’homme.

Targeting is done by incorporating certain molecules, such as antibodies, onto the surface of the nanoparticle. Antibodies bind specifically to proteins on the surfaces of cells, such as in tumors. The antibody-nanoparticle is an advantage over traditional antibody–drug combinations because far fewer antibodies are required. Each nanoparticle needs just a few antibody molecules on its surface, compared to a 1:1 ratio for naked drugs to antibodies. “The advantage of this is that we can deliver 15,000 drug molecules in a 100-nanometer particle with a limited number of antibodies on the surface,” said Prud’homme.

Applications:

The team and its collaborators have been experimenting with developing “drug cocktails” that deliver multiple drugs from the same nanoparticle. This could be useful in cancer therapy and tuberculosis, disease that require multiple drugs to be administered to patients. Flash NanoPrecipitation is being explored as a way to deliver exploratory therapies such as siRNA. It is also possible to tune the size of the particle so that it is small enough to travel through capillaries in the lungs, one particle at a time, to deliver drugs for the treatment of lung cancer.

In addition to drug delivery, another promising use of the technique is in the creation of research and diagnostic molecules that enables the tracking of disease progression. In place of drugs, the nanoparticles can contain fluorescent compounds that emit light at ideal wavelengths (650 to 1000 nanometers) for biological imaging. Tissues of the body do not absorb much light at these wavelengths, so the light penetrates deeply into the tissue, yet can still be detected by instruments.

 Fluorescently labeled imaging molecules encased in the nanoparticles and bearing antibody targeting systems could allow the particles to travel to tumors or other disease sites. This offers researchers the ability to detect and monitor tumors inside the body without having to surgically expose the tumor. The first application could be in cancer research, where a single research mouse or other laboratory animal could be followed for its tumor growth, replacing the common method of inducing cancer in a group of several mice and euthanizing them sequentially to monitor tumor growth. This method would reduce the overall number of animals used as well as decreasing the inter-animal variability and addressing ethical concerns.

Inspiration: Researchers would like to target drugs and diagnostic imaging molecules directly to the location of disease or injury. Since many anti-cancer agents are toxic there is a need to understand whether the targeted nanoparticles are delivering the drugs successfully to the tumor site and not to healthy tissue.

Collaborators: Flash Nanoprecipitation was developed with National Science Foundation funding and has resulted in invention disclosure with collaborators including Christopher Macosko and Tom Hoye, professors of chemical engineering and materials science and chemistry at the University of Minnesota, and Rodney Fox, professors of chemical and biological engineering at Iowa State University. Prud’homme collaborates with Pat Sinko at Rutgers University and Howard Stone on drug delivery to the lungs. At Princeton, Prud’homme collaborators include Howard Stone on lung cancer studies and Jamie Link on nanoparticle targeting and DNA sequencing with nanoparticles. The research includes both graduate and undergraduate student. “Our students are really being involved in cutting edge research that brings them in contact with startup companies and biotech companies,” said Prud’homme. “That is one of the things that Princeton does really well.”

Commercialization status: Prud’homme’s research group has attracted a number of collaborators, including Merck for developing siRNA drugs in nanoparticle form, Amgen for placing peptides in nanoparticle form, Celator Pharmaceuticals for targeted delivery of cancer drugs, Sequella for the treatment of tuberculosis, the National Institutes of Health for wound healing therapeutics and Optimeos for whole animal imaging. “Our specialty is nanoparticle engineering,” said Prud’homme. “We look for collaborators who have knowledge of the needs in therapy and drug delivery where we can contribute. The phrase ‘translation from engineering to medical therapy’ defines our vision as a group.”

Patents have been filed on Flash NanoPrecipitation and associated technologies, and options and licenses have been negotiated.