Poly(lactic-co-glycolic acid) microparticles in fibrin glue for local, sustained delivery of bupivacaine

Abstract To control postoperative pain, a bolus solution of anesthetic drugs is often injected locally, which, however, is limited by short-term drug efficacy and low bioavailability. To resolve this, we propose a composite formulation of bupivacaine-loaded poly(lactic-co-glycolic acid) microparticles (BPC-MPs) and fibrin glue. We prepared the BPC-MPs using the emulsion method and formulated them with fibrin glue to produce FG_BPC-MPs. We performed in vitro drug release experiments for 35 days with the formulations in pH 7.4 phosphate buffered saline (PBS) at 37 ℃. To evaluate in vivo pain-relief efficacy, the pain-induced animals via L5-spinal nerve ligation were treated with FG_BPC-MPs, as well as the control formulations, and the paw withdrawal latency was evaluated with the von Frey filament test. The FG_BPC-MPs exhibited a sustained drug release with a reduced initial burst for up to 35 days. When tested in vivo , a dramatic increase in paw withdrawal threshold was observed during the entire 10-day testing period, suggesting that the pain-relief efficacy was improved and prolonged compared with that for the other control formulations. The FG_BPC-MPs loaded with bupivacaine can be a promising formulation for the treatment of local, persistent pain after surgery.