The Development of Injectable Hydrogels for the Management of Chronic Pain

Pain medication is typically administered in one of three forms: bolus injection, tablet, or intravenously (IV). Some of these methods of introducing the drug into the body can cause dangerously high increases of concentration of the drug in the bloodstream and may be only effective for short windows time during which the patient is actually relieved of their pain. There is a need to develop controlled sustained release systems that may overcome these issues. One such method of controlled drug delivery is in the form of a hydrogel that is filled with a drug and capable of releasing the drug over the course of days or weeks. Most hydrogels are formed through a chemical reaction or with a photochemical reaction making it difficult to place the hydrogel inside a patient without a surgical procedure. In this presentation, we will describe our efforts to develop a set of materials and reaction conditions to develop a hydrogel that is injectable and solidifies within a few minutes of injection. When mixed with buffer at 37°C the biocompatible polymers polyethylene glycol diacrylate and ethoxylated trimethylolpropane tri-3-mercaptopropionate (ETTMP) undergo a Michael addition reaction to form a solid crosslinked hydrogel. We show evidence that the purity of the ETTMP is critical to the reaction success and we developed a method to purify ETTMP suitable for making the hydrogel.  Finally, we loaded the hydrogel with a model drug, methylene blue, and followed the release of dye over the course of about nine days.