Faculty Sponsor's Department(s):
Targeted drug delivery is a method of bringing higher concentrations of anti-cancer drugs directly to the targeted site in the body while simultaneously attempting to minimize interaction of cytotoxic drugs with healthy tissue. Paclitaxel (PTXL), a small molecule drug, is one of the most widely-used anti-cancer agents for the treatment of breast cancer and ovarian cancer. However, PTXL has poor water solubility and low bioavailability due to its hydrophobicity. EndoTAG (™), a liposome-based formulation to deliver PTXL, is currently in phase three clinical trials in Belgium. EndoTAG (™) is a known three component formulation consisting of DOPC, DOTAP, and PTXL. We want to understand what benefits come from using these components in the trademarked formulation, and how altering the formulation may enhance drug delivery properties. Polyethylene Glycol (PEG) is a hydrophobic polymer ubiquitously used to coat nanoparticles of all types for drug delivery. This coating is necessary to allow enhanced therapeutic delivery and to augment in vivo retention time. We want to understand if including PEG lipids in the liposome formulation has an effect on the particles’ ability to solubilize PTXL. We can study this further by checking how this varies as a function of PEG length and the amount of PEG-lipid that is incorporated in liposomes. During our experiments, we varied the composition of liposomes in EndoTAG (™) to contain different amounts of PTXL in particles with and without a PEG polymer coating. The series of samples were analyzed using Differential Interference Contrast (DIC) Microscopy to optically observe phase separation of PTXL into crystals and thus determine the relative duration of stability imparted by different membrane properties.