Researchers Developing Technique to Make Injectable Medicine Safer

The goal is to reduce serious allergic reactions and other side effects from a variety of drugs including anti-cancer medicine, testosterone and other drugs administered through a needle.

The innovative process removes potentially harmful additives — primarily soapy substances known as surfactants — from common injectable drugs. The breakthrough is described in a study “Therapeutic Surfactant-Stripped Frozen Miscelles,” that was published in the journal Nature Communications.

“We’re excited because this process can be scaled up, which could make existing injectable drugs safer and more effective for millions of people suffering from serious diseases and ailments,” says Jonathan F. Lovell, PhD, assistant professor of biomedical engineering and the study’s corresponding author.

Pharmaceutical companies use surfactants to dissolve medicine into a liquid solution, making it suitable for injection. While effective, the process is seldom efficient. Solutions loaded with surfactant and other nonessential ingredients can carry the risk of causing anaphylactic shock, blood clotting, hemolysis and other adverse side effects.

Researchers have tried to address this problem in two ways, each with limited degrees of success.

Some have taken the so-called “top down” approach, in which they shrink drug particles to nanoscale sizes to eliminate excess additives. While promising, the method doesn’t work well in injectable medicine because the drug particles are still too large to safely inject.

Other researchers work from the “bottom up,” using nanotechnology to build new drugs from scratch. This may yield tremendous results; however, developing new drug formulations takes years, and drugs are coupled with new additives that create new side effects.

The technique under development by Lovell’s team of researchers differs because it improves existing injectable drug-making methods by taking the unusual step of stripping away excess surfactant.

In laboratory experiments, researchers dissolved 12 drugs one at a time into a surfactant called Pluronic. The dissolved drugs included cabazitaxel, an anti-cancer drug; testosterone; and cyclosporine, an immunosuppressant used during organ transplants.

Then, by lowering the solution’s temperature to 4 degrees Celsius — most drugs are made at room temperature — they were able to remove excess Pluronic via a membrane, resulting in drugs that contain 100 to 1,000 times less excess additives.

“For the drugs we looked at, this is as close as anyone has come to introducing pure, injectable medicine into the body,” says Lovell. “Essentially, it’s a new way to package drugs.”

The findings are significant, he says, because they show that many injectable drug formulations may be improved through this easy-to-adopt process. Future experiments are planned to further refine the method, Lovell says.

Additional UB faculty and staff authors on the paper are:

• Paschalis Alexandridis, PhD, UB Distinguished Professor in the Department of Chemical and Biological Engineering
• Javid Rzayev, PhD, associate professor of chemistry
• Dinesh K. Sukumaran, PhD, director of the Magnetic Resonance Center in the Department of Chemistry

Other authors of the paper include the following UB students and scientists:

• Yumiao Zhang, PhD candidate in chemical and biological engineering
• Wentao Song, research assistant in biomedical engineering
• Upendra Chitgupi, PhD candidate in biomedical engineering
• Jumin Geng, research technician in biomedical engineering
• Jasmin Federizon, PhD candidate in chemistry
• Hande Unsal, postdoctoral fellow in chemistry