Breakthrough Curves for Ettmp Purification with Alumina Oxide

Biomaterials can be used in the advancement of targeted drug-delivery methods. Hydrogels are one of these useful drug delivery vehicles suitable for a range of drugs and therapeutic proteins. However, ultraviolet-cured and thermally-cured hydrogels suffer from drawbacks when prompted to control drug release in vivo because they need to be implanted. Degradable injectable hydrogels that cure in-situ are an emerging alternative that make clinical sense. Albeit there are some issues with these systems because there needs to be further research conducted to better understand them before broader adoption. In this poster, there’s an exploration of the dependence of the curing kinetics with a range of factors for a thiol conjugate Michael Addition reaction used in the hydrogel system containing Poly(ethylene glycol) diacrylate (PEG-575-DA) and Ethoxylated trimethylolpropane tri-3-mercaptopropionate (ETTMP, Thiocure 1300).

The synthesis and curation of these gels are based on using a calculated volume of precursors resulting in an equimolar stoichiometric ratio of thiol and acrylate groups. Varying precursors were used to determine the most effective and consistent hydrogel curing. However, precursor impurities have a large effect on the cure time. This is relevant because the material, as shipped, degrades over time releasing mercaptopropionic acid (MPA). Subsequently, this impurity must be removed for any curing to take place at a pH of 7.4. Correlating MPA concentration to cure time, we can remove excess MPA effectively utilizing basic alumina. There is a correlation between the height of the column and ratio of alumina to ETTMP to remove MPA. When purifying in a 20 mL syringe, the height needs to be a minimum of 1.5 in., and a 2:1 ratio of alumina to ETTMP was found to remove MPA to trace levels. We attempted to determine breakthrough curves for MPA in an alumina column using titrations to gauge the pH of the purified ETTMP. Multiple runs of purification were tested with varying heights of alumina to determine breakthrough curves. It was found that the column slowly reacts with the ETTMP and eventually reduces the flow rate to zero before the MPA breaks through. Therefore, with low MPA concentrations, a hydrogel cures in about 1.5 min. Another number of tests were performed to analyze the mechanical properties of the hydrogel during its curation period. Dynamic rheology was used to determine the exact gelation time, which was confirmed by a frequency sweep to ensure the data was within the linear viscoelastic range.