A moldable and biodegradable dental material was designed for customized placement and sustained delivery of bupivacaine (BP) within an extraction cavity. Microparticles comprising poly(lactic-co-glycolic acid) (PLGA) containing BP were generated via solvent-evaporation and combined with absorbable hemostat Gelfoam (R). Kinetics of drug release were evaluated by in vitro dialysis assays, showing higher release within the first 24 hours, with subsequent tapering of release kinetics. Formulations of Gelfoam (R) and BP-PLGA microparticles (GelBP), with three targeted dosing profiles (0.25, 0.5, and 1 mg/kg/day), were evaluated alongside acute subcutaneous BP injections (2 mg/kg) to determine analgesic efficacy in a rat model of tooth extraction pain. Molar extraction resulted in mechanical and thermal cold hyperalgesia in male and female rats. GelBP outperformed acute BP in blocking post-surgical dental pain, with the 0.25 mg/kg GelBP dose preventing hypersensitivity to mechanical (p <0.01) and thermal cold stimuli (p = 0.05). Molar extraction also resulted in decreased food consumption and weight. Males receiving acute BP and 0.25 mg/kg GelBP maintained normal food consumption (p <0.002) and weight (p <0.0001) throughout 7 days. Females, receiving 0.25 mg/ kg GelBP maintained weight on days 5-7 (p <0.04). Customized, sustained release formulation of anesthetic within a tooth extraction cavity holds potential to eliminate post-operative dental pain over several days.
A moldable sustained release bupivacaine formulation for tailored treatment of postoperative dental pain
Shepherd, S. D., O'Buckley, S. C., Harrington, J. M., Haines, L. G., Rothrock, G. D., Johnson, L. M., & Nackley, A. G. (2018). A moldable sustained release bupivacaine formulation for tailored treatment of postoperative dental pain. Scientific Reports, 8(1), . https://doi.org/10.1038/s41598-018-29696-w
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