Dual-tunable liquid crystal-forming system enables sustained ropivacaine delivery for prolonged local analgesia.

Postoperative pain management remains a challenge in clinical practice. Traditional local anesthetics often require repeated administration due to their short duration of action, which increases the risk of systemic toxicity and nerve damage. Herein, we developed an injectable, dual-tunable, low-ethanol lyotropic liquid crystal-forming system (LCFS) for sustained local ropivacaine (Rop) release, achieving long-lasting analgesia. Upon injection, the precursor solution transformed into a gel in situ, forming a drug reservoir for sustained release of Rop. The system was optimized by adjusting the ratio of phosphatidylcholine to glyceryl monooleate and the content of corn oil, enabling dual modulation of drug release kinetics. The optimized Rop@LCFS formulation demonstrated sustained release for up to 7 days, with an initial burst followed by controlled release. Compared with commercial bupivacaine liposome injection, Rop@LCFS exhibited 8-fold prolongation of effective sensory blockade duration in the rat sciatic nerve block model, while maintaining over 12 h of sustained analgesia in the subcutaneous infiltration anesthesia model. The formulation also displayed favorable biodegradability and biocompatibility both in vitro and in vivo. The Rop@LCFS features easy preparation, sustained release, and biocompatibility, offering potential for clinical translation and long-acting local anesthetics development.