No-clump proteins may change drug delivery

U. TEXAS-AUSTIN (US) — A new form of proteins could improve treatments for cancer and other diseases, and deliver drugs to patients more effectively, researchers report.

The protein formulation strategy, discovered by chemical engineering faculty members and students in the Cockrell School of Engineering at the University of Texas at Austin, offers a new and universal approach to drug delivery—one that could revolutionize treatment of cancer, arthritis, and infectious disease.

“We believe this discovery of a new highly concentrated form of proteins—clusters of individual protein molecules—is a disruptive innovation that could transform how we fight diseases,” says Keith P. Johnston, a chemical engineering professor.


The research, led by Johnston, Thomas Truskett, professor of chemical engineering  and assistant professor Jennifer Maynard, appears in ACS Nano journal.

“The real challenge in developing therapeutics is how do you deliver them to patients,” Maynard says.

Typically, protein biopharmaceuticals are administered intravenously at dilute concentrations in a hospital or clinic. Scientists and engineers have long tried to produce safe drugs at higher concentrations so that a patient could self-inject the drugs at home, similar to an insulin shot.

But doing so has been stymied by the fact that proteins, in high-concentration formulations, form aggregates that could be dangerous to patients and gels that cannot be injected.

The research team has introduced a new physical form of proteins, whereby proteins are packed into highly concentrated, nanometer-sized clusters that can pass through a needle into a patient to treat disease. The novel composition avoids the pitfalls of previous attempts because drug proteins are clustered so densely that they don’t unfold or form dangerous aggregates.

“This general physical concept for forming highly concentrated, yet stable, protein dispersions is a major new direction in protein science,” Johnston says.

Through the research, the team formed protein nanoclusters in water simply by properly adjusting the pH (to lower protein charge) and adding sugar to crowd protein molecules together. Upon dilution, or subcutaneous injection into a mouse, the proteins separate back into individual stable molecules with biological activity.

Once injected, the protein in the bloodstream attacks targeted cells and tumors similarly as for protein delivered via intravenous therapy.

Since the researchers began their collaboration in 2004, the nanoclusters they developed have been successfully tested on mice, multiple major pharmaceutical companies are pursuing them, and three patents have been filed.

The research is funded by the National Science Foundation, the National Institutes of Health, the Welch Foundation, and the Packard Foundation. Starting in 2012, two major pharmaceutical companies will fund the work.

More news from the University of Texas at Austin: