September 11, 2012
Professor Valdimir Torchilin has been working with liposome drug carriers since the field was in its infancy.We all know about oil and water: They don't mix.
Phospholipids, however, are the two-sided exception that proves this rule. One side of a phospholipid molecule loves to hang out in water, while the other turns away from it like the most timid housecat.
In the mid-1960s, Dr. Alec Bangham discovered that when dispersed in water, phospholipids aggregate into closed, spherical vesicles called liposomes. The water-loving sides form a protective barrier around their oily neighbors in what's called a lipid bilayer (the membranes that surround our cells are made of the same stuff).
"You cannot list too many systems with such a nice set of properties," said Vladimir Torchilin, a University Distinguished Professor at Northeastern University, who recently received the Bangham Award for his outstanding contributions to the study of liposomes.
"They are easy to make and easy to scale up," he added. "You can pretty easily load them with many types of drugs. They are completely biocompatible. And they are stable enough to exist for a few hours in the body."
For these reasons, Torchilin and his colleagues quickly realized that liposomes would make great carriers for targeted drug delivery. By the late-1970s they demonstrated that these convenient creations could be functionalized with proteins that discriminately home to specific cell types, such as cardiac or cancer cells. Like microscopic "passenger trains," Torchilin explained, liposomes could be designed to transport drugs to a desired final destination.
Today, Torchilin's research focuses on cancer drug delivery. Instead of passenger trains, the liposomes act like Trojan Horses, delivering the toxic effects of chemotherapies directly to the cells we want to destroy. Because this approach brings a higher concentration of drug directly to the tumor, Torchilin explained, it "allows you to decrease the total dose you administer, which in turn reduces the level of cytotoxic response from normal tissue."
The first liposomal drugs, which were approved in the mid-1990s, focus on a characteristic of the vasculature that supplies tumors. "Tumor blood vessels are leaky," said Torchilin. "And the particles fall through the blood vessels into the tumor tissue." But, he explained, this still leaves room for the drug to get accidentally directed to healthy tissue.
Torchilin and his colleagues are currently developing platforms that induce cancer cells to directly internalize liposomes. When the vesicles break down, their contents are released exclusively inside the cell. While it's still not foolproof, this kind of active targeting allows clinicians to deliver much more effective treatments.
The drug doxorubicin, for example, has been used for nearly half a century. But it is highly toxic to many cell types including heart cells. Cardiac disease — a devastating disease in its own right — is a side effect of the drug. But once inside a liposome, doxorubicin comes into contact with healthy cells much less frequently. This also allows for higher dosages, which in turn improves the drug's already good effectiveness.
Overall, Torchilin said, "the goal of the lab is to save lives from time to time." Cancer is a highly nuanced disease and targeted drug delivery is still not perfect, says Torchilin, but in the last several decades it has come quite a long way. He's confident his innovations will continue to improve delivery platforms.
Dr. Torchilin will present a lecture on his accomplishments in the area of liposome research at the Liposome Research Days meeting in Hangzhou China on October 12, 2012.