Vectors for gene therapy and improving drug solubility
By Nicolas Huguet, CBB Biographer
July 21, 2015
In the pharmaceutical industry, everyone knows that developing a drug that will actually find its way to patients is difficult to say the least. Many recent compounds which have the potential to treat diseases are not marketable because they can’t be delivered properly. This is a huge loss for people across the world.
CBB member Shawn Wettig’s research in emulsion systems may help to unlock the potential of these new drugs. Indeed, the main characteristic that makes these drugs tough to deliver is their low solubility in water. He is currently developing emulsion systems based on different combinations of surfactants and polymers for developing new formulations for these types of drugs. The aim of his project is to find the right formulations so that a high enough concentration of the compound can be found in the volume of a soft gelatin capsule. He has partnered with Accucaps Industries Ltd. a leading softgel manufacturer in Ontario to tackle this problem. Their collaboration, which he describes as synergistic, may allow for new drugs to be made available to patients and for a higher therapeutic effectiveness of existing drugs.
Another research project he is working on involves the development of polymer-based nanoparticles for delivering DNA during gene therapy. The nanoparticles he is testing are made of positively charged surfactants and neutral polymers. He is looking to develop a different type of nanoparticle depending on the tissue that is targeted for the gene therapy. Examples include functionalizing the polymers with a bisphosphonate because it has affinity with bone tissue, or functionalizing the polymers with folic acid to target ovarian cancer tumors (which have a high expression of the folic acid receptor). In each case, the functionalized nanoparticle is a vector for the DNA to get to the right cells in the body.
One of the challenges in his research is to optimize the size of the polymers. Indeed, if they are too big, they will not be able to get to the targeted cells. Shawn Wettig says that once they have optimized these molecules for something big like DNA, it should be relatively easy to take the same systems and apply them to smaller molecules. His hope is that he can apply the same technology to small molecules like therapeutics, chemotherapeutics and other drugs.
There are many unanswered questions in the field of gene therapy such as: how can we improve expression, how can we control expression, how safe is gene therapy and how exactly does the DNA get into the cell. He hopes his research will lead to answering some of these questions and that the expertise and knowledge he is generating will help other researchers advance their research as well.