Molding Technique Improves Nanoparticle Production

A team of chemists from the University of North Carolina at Chapel Hill (UNC, Chapel Hill, NC) has developed a new method that can reliably produce organic nanoparticles of the same size and shape, according to the university.

The technique uses micrometer-sized ice-cube-tray–like molds. Researchers select a liquid carrier from a variety of hardenable options out of which to make the nanoparticles and pour it into the molds. A small force is applied between the tray and another surface. After the liquid is converted into a solid, the chemists then open the mold and harvest the particles. Depending on the liquid used, monodisperse nanoparticles can be produced within 30 seconds. Because the technique eliminates variations in particle size, particle size distribution, or particle shape distribution, says Joseph M. DeSimone, PhD, a UNC chemical engineering professor, “It’s a breakthrough in particle technology that raises the bar…There’s never been a nanoparticle production process that can control these factors.”

A key aspect of the technology is the material out of which the trays are made: a photocurable perfluoropolyether (PTFE) that maintains a liquid form at room temperature. To make the trays, the PTFE is poured over a master template with monodispersive cavities of the appropriate nanoscale shapes. The trays are cured into a solid form. Because the particles adsorb onto the mold and won’t slide off, the UNC scientists can coat the particles with a ligand using a dipping technique.

According to DeSimone, a UNC chemical engineering professor, “The molding process is very gentle and is very compatible with proteins and small-molecule therapeutics. We’ve demonstrated that we can add those types of cargo to the liquid to be molded as a delivery method.” Approximately 30–40% of the particle can be comprised of a cargo that is wrapped in the matrix (i.e., the base material used to make the particle).

Whereas most nanoparticles are made out of metal or metal oxides, the UNC technique enables the matrix to be an organic, bioabsorbable, biocompatible, biodegradable substance. For example, the scientists recently molded nanoparticles out of a polylactide, a fully bioabsorbable, FDA-approved material for making sutures.

To remove the cargo-carrying particles from the mold, scientists coat the particles (most are hydrophilic) with a thin sheet of water, which is then frozen. The thin, frozen sheet is lifted off with all the particles in it. At this point, the particles will be in a very concentrated solution with their cargo inside.

Though the scientists are currently working with small batches, the patented technology has been licensed to Liquidia Technologies, Inc., (Research Triangle Park, NC), a company focused on developing a continuous process for making the large-scale quantities of particles using a roll-to-roll technology. “It looks like candy dots on wax paper. You just scrape them off with a blade or use liquid or ultrasound methods for separating them,” DeSimone explains. The company is currently seeking partners to help develop the technology for full-scale production.

–Kaylynn Chiarello