2024 AIChE Annual Meeting
Modifying Poly(beta-amino ester) Hydrogel Formulations to Achieve Sustained Release of Bupivacaine Anesthetic
The current standard of care to treating post-operative pain is opioids. Opioids are powerful pain blockers but are a highly addictive substance responsible for many overdose deaths. Nerve blocks can reduce opioid use but typically last no more than 4 hours with an anesthetic, Bupivacaine, injection. Another option is the sustained-release nerve block, Exparel®, which only provides pain management for 72 hours (3 days). The challenge with Exparel® is that facial surgery requires at least 7 days of post-operation pain relief, which means that the highly addictive opioids are still prescribed. The aim of this work is to improve upon the current sustained release of nerve-blocking anesthetics to reach the needs of more patients. In this research, a variety of formulations and structures of Poly(beta-amino ester) (PBAE), a biodegradable hydrogel, have been tested to achieve a more sustained release of Bupivacaine, which is an anesthetic with a long half-life. The PBAE used was formed from diethylene glycol diacrylate (DEGDA) or Poly(ethylene glycol) diacrylate (PEGDA) and isobutylamine (IBA). All formulations kept a molar ratio of 1.2:1 diacrylate to amine, but the molar ratios of the diacrylates were differentiated: molar ratio 3:1 DEGDA to PEGDA and a homopolymer of DEGDA. The purpose of having a formulation with just DEGDA as the diacrylate is to increase crosslinking, due to its shorter chain length within the PBAE, to have a more sustained release over time. The structures of each formula were tested in a particle format and a variety of disc thicknesses. Results from release studies showed that utilizing the homopolymer formulation had a more sustained release of Bupivacaine over a 7-day period in comparison to the copolymer formulation. However, this release profile was only seen in disc form, and did not extend to microparticles. Overall, this suggests that future developments will need to keep the integrity of the hydrogel structure to achieve a sustained release with this formulation.