New packaging developed at CMU for drug delivery

Modern medicine can do some amazing things. From shocking hearts back into rhythm to eradicating disease altogether, medicine seems to be a field of ever-growing possibility. However, when considering diseases such as cancer, where the enemy is not a foreign invader but the body’s own tissues, effective treatments require a little more engineering, which is where targeted drug delivery comes into play.

Targeted drug delivery is a very complicated process, especially in the case of cancer, where it is difficult to distinguish between mutated cells and healthy ones. Cells receive stimulation from the outside environment via receptor proteins located in their membranes. There are no cancer-cell-specific receptors, which in an ideal situation could be used to effectively treat cancer cells. This makes it difficult to specifically target cancer cells with medication and leave the healthy cells untouched. Many drugs tend to interfere with the parts of a cell crucial for division, which also means that they will target the cells that tend to divide more quickly — hair, skin, and bits of the digestive system. This is one reason why smart drug delivery is being researched — to stop wrongfully killing healthy cells.

There are still many large questions surrounding this treatment method, including how to get drug molecules into cells and how to differentiate between healthy and diseased cells. While some factors are not quite set in stone, researchers from Carnegie Mellon University, the Colorado School of Mines, Golden, and U.C. Davis have partnered to tackle a relatively more concrete project: engineering the structure of the “packages” within which drugs would be contained — liposomes.

Liposomes are the structures that surround the drug and carry it through the body. Liposomes are made up of phospholipids, the same molecules that make up a cell’s membrane. They are an important factor in the viability of targeted drug delivery because they have to be structurally sound; if they are not, doctors run the risk of having them burst inside patients, spilling their destructive contents in the body and leading to internal damage.

This project was a multi-scaled study, meaning that three different teams targeted the problem from three different microscope resolutions. The resolution determines the properties and science considered by the particular team — will they look at the liposome’s structure at a magnification which privileges chemistry (atomic/molecular levels), or will they take a coarser look and privilege physical properties?

The Carnegie Mellon researchers, led by Professor Markus Deserno of Carnegie Mellon’s Physics Department and Dr. Mingyang Hu, a PhD candidate in computational biophysics, focused on the structure at a coarse level. This means that they looked at the problem from a physical perspective, applying the study of physics to their computational models and examinations.

They started out with a hub and spoke model, the same design as an old carriage wheel: the drug molecule in the center, polymeric tethers which would bind to the drug as the supportive spokes, and the phospholipids which would comprise the surrounding layer, or the wheel itself.

The team concerned themselves with the pragmatics of liposome creation, since one of the overarching goals of their research is to produce the liposomes for clinical use. They focused on the liposome’s dispersity, or the uniformity of the system, and, according to Deserno, “how uniform does it have to be not to disperse, in order to work?” The results were encouraging enough that production would not be prohibitively expensive, and the system will hold just fine in theory.

The team was also concerned with the production process’ role in creating liposomes. For simple liposomes without the structural design necessary for carrying drug molecules, Deserno said that “[their size] depends on the production process. But this isn’t the case with our structure. The size of the liposome is dictated by the physics. It’s the choice of design parameters, like how many polymers, how long they are, et cetera.”

This means that the theoretical structure is much more easily producible, good news for those who would actually construct them.

“I’m the guy at Amazon who packages things nicely so they don’t get broken,” said Deserno.

The researchers developed a theoretical, robust package for drug delivery. Deserno maintained that while the findings were “pure theory and computational study,” the theories should be sound enough that when another lab attempts to produce the liposomes using these blueprints, it should work swimmingly.