Breast cancer treatment methods such as chemotherapy, hormone therapy and radiation therapy can cause adverse side effects and may not be well tolerated by patients. One such treatment, the chemotherapy drug 5-Fluorouracil (5-Fu) is used in the treatment of several different cancer types, including breast cancer. Currently, it is administered intravenously, directly into the bloodstream, but researchers from Sardar Vallabhbhai National Institute of Technology and the University of Strathclyde are working with ISIS scientists to explore transdermal delivery methods of 5-Fu, where the drug formulation is applied directly to the skin surface using hydrogels.
Transdermal drug delivery (TDD) is advantageous because the skin provides a large surface area for drug absorption and avoids some adverse responses in the body. However, if the drug has large or hydrophilic molecules like 5-Fu does, it cannot easily go through the skin barrier. To improve penetration of the drug, a chemical penetration enhancer is often added to the formulation, working by disrupting the lipid bilayer of the outer layer (strateum corneum) of the skin. Effective TDD drugs also need to be highly soluble in the body’s fluids, something that most commercially available drugs lack. To overcome this, ionic liquids (ILs) can be used as solvents. They consist of choline partnered with amino acids, fatty acids or amides. Recent work has developed IL-based hydrogels known as ionic hydrogels, which have all the strengths of hydrogel solutions: biocompatibility, self-healing abilities, adhesiveness, high drug loading capacity and sustained release at the target site.
In this study, the team developed an ionic hydrogel with a choline amino acid based IL called ([Cho][Gly]) and used the fatty acid oleic acid (OA) as a chemical penetration enhancer. They characterised the mixture using various techniques, including Small Angle Neutron Scattering (SANS) on Sans2d at ISIS to understand the mechanisms of the ionic hydrogel formation and the structure of aggregates formed within it. They observed four different types of aggregate as the concentration of OA and pH were increased, transforming from ellipsoidal to cylindrical and then to worm-like structures before becoming a hydrogel.
The primary objective of the research was to design a transdermal drug delivery system that is appropriate for the 5-Fu drug. Using a variety of technical methods, including SANS, the researchers concluded that the [Cho][Gly]/OA based hydrogel has the potential to be a biocompatible and effective drug delivery system for transdermal delivery of hydrophilic chemotherapeutic drugs, including 5-Fu and could be applied to treatment of other diseases in the future.
