Mimicking the screening process that drug developers use to find the optimal candidate molecule, researchers at BIND generate hundreds of versions of nanoparticles for each drug and then screen each to find those that can survive in the bloodstream the longest and have the best tissue-targeting capabilities. By slightly varying the concentrations of each of the three components, the researchers can generate particles that have a different size, surface charge, and concentration of targeting molecules on its surface.
“It’s a fine balance between stealthiness and targeting,” says Jeff Hrkach, vice president of pharmaceutical sciences at BIND. “With too much of the targeting ligand, the particle will get cleared from the bloodstream.” While scientists have traditionally tried to pack as much of this marker as possible onto the nanoparticle in order to enhance its targeting prowess, Langer and Farokhzad found that fewer of these molecules actually work better.
So far scientists at BIND have tested the technology with 15 different drugs for cancer, cardiovascular disease and inflammatory diseases, but are focusing first on chemotherapeutics. Testing the drug-laden particles in mice engineered to have human tumor cells, researchers showed that animals treated with the nanoparticles had a much higher concentration of drug in the tumor–up to 20 times higher–12 hours after delivery than did animals given the naked drug. The nanotech version of the drug was also able to stop the growth of breast, prostate and lung tumors more effectively than either the drug alone or the drug delivered via nanoparticles lacking the targeting molecules.
BIND scientists have also enhanced circulation time from three to six hours to 24 to 72 hours, according to results presented last month at a conference at the National Cancer Institute. “They showed some really impressive circulation times,” says Joseph DeSimone, a chemist at the University of North Carolina, Chapel Hill, who is not involved with the company. “It looked much longer than other things I’ve seen in the literature.”
For its planned tests of the technology next year on human subjects, the company has not yet specified the type of cancer or the chemotherapy drug to be used. It is, however, scaling up the manufacturing process in order to make enough of the particles for clinical tests.
In addition to existing drugs, BIND is working with undisclosed pharmaceutical companies to determine whether candidate drugs, including those that might have been shelved because of problematic side effects or other issues, might be enhanced or revived with targeted nanoparticle delivery.