Chemotherapy drugs are known as much for their negative side effects as for their ability to treat cancer. That’s because the small molecules used to kill tumor cells are also toxic to healthy cells. Targeted drug delivery, a method that came of age in the 1970s, aims to diminish chemotherapy’s side effects by delivering drugs directly into the diseased cells, leaving the healthy ones unharmed.
One of the original scholars in this field is Vladimir Torchilin, Distinguished Professor of pharmaceutical sciences at Northeastern University, who recently received the Journal of Drug Targeting‘s 2012 lifetime achievement award. The journal is among the leading compendia of drug targeting scholarship, and its award recognizes scientists who have made exceptional and sustained contributions to drug delivery and targeting, according to the journal’s editor-in-chief, Saghir Akhtar of Kuwait University.
Torchilin is quick to assert that his achievements in the field have been part of a larger, collaborative effort with contributions from many researchers over several decades. He said the other recipients of the award are among his closest colleagues and friends.
In recognition of the award, the Journal of Drug Targeting will publish a special issue highlighting Torchilin’s work and the research it has inspired.
Torchilin, the director of Northeastern’s Center for Pharmaceutical Biotechnology and Nanomedicine, is perhaps most well known for his work developing liposomal carriers, vesicles made of a lipid bilayer similar to the one that surrounds human cells. This is the type of carrier used in one of the few targeted cancer treatments currently on the market.
Torchilin said tumor cells have many more receptors for particular molecules than healthy cells. For example, tumor cells can have at least a dozen times more receptors for folic acid than a noncancerous cell. As a result, when carriers like Torchilin’s liposomes are tagged on the surface with folic acid, they will end up binding to cancer cells much more often than healthy cells. This is the rationale behind targeted cancer therapies.
Targeting defective cells in diseases other than cancer is also very important. For example, myocardial infarction is characterized by cardiac cell damage. An earlier method developed by Northeastern pharmaceutical sciences professor Ban An-Khaw allows for targeted delivery of imaging agents to such cells for infarct visualization, Torchilin explained. “But the absence of a cell could be targeted, too,” he added.
When endothelial cells lining the inner wall of a blood vessel are lost as a result of infection or injury, thrombi and atherosclerotic lesions can form. Targeting certain drugs to such areas can prevent thrombus formation and assist endothelium re-growth.
Torchilin’s lab developed yet another method for targeting drugs to specific cell locations. This is particularly relevant for diseases that are characterized by failures in specific organelles, such as lysosomal storage diseases, a collection of about 40 inherited diseases that affect about one in every 5,000 to 10,000 people worldwide.
The lysosome is often considered the cell’s “recycling center” because it contains a variety of enzymes that work to break down unwanted particles in the body and then turn them into useable forms. Lysosomal storage diseases result when one or more of these enzymes are absent because of a genetic defect. Torchilin’s method allows for the targeted delivery of the depleted enzymes directly to the lysosome.
“The algorithm is the same for each individual disease,” said Torchilin. “You just have to deliver different enzymes.”
The current treatments for lysosomal storage diseases are very expensive. “If you can develop a system that will allow you to utilize much less of the active enzyme, the delivery system will be simpler and more cost effective and you could save more lives,” Torchilin said.