In Vitro and In Vivo Evaluation of Lidocaine Hydrochloride-loaded Injectable Poly(Lactic-co-glycolic Acid) Implants

Background: Effective postoperative pain control is essential for the recovery of surgical patients. However, long-term analgesia can seldom be achieved with the existing medications. The injectable implants prepared by biodegradable polyesters can be conveniently used during the surgery and slowly release analgesics near the operative incision for a long period. Method: In this study, we prepared lidocaine hydrochloride (Lido-HCl)-loaded injectable poly(lacticco- glycolic acid) (PLGA) implants for prolonged analgesia. The optimized formulation of this injectable implant sustained drug release for up to 5 days, with a cumulative release of 85.8%±1.9% in the in vitro release experiment. Results: The in vivo release of the implants in rats showed good consistency with the in vitro release. The pharmacokinetics of Lido-HCl implants in the thigh muscle of rats was evaluated, and the AUC0-120 h of the Lido-HCl implant was 11.4 times that of Lido-HCl solution, indicating a good sustained release function of the implant. The pharmacodynamics of Lido-HCl implants was measured by the hot plate test. The Lido-HCl solution blocked the sciatic nerve of rats for less than 4 h, while the Lido-HCl implant efficiently blocked the nerve for approximately 120 h. Conclusion: These results demonstrated that the PLGA-based injectable implant is a suitable carrier for postoperative pain control.