Structural characterization and enhanced analgesic efficacy of a bio-responsive lyotropic liquid crystal Quject® gel for long-acting ropivacaine delivery.

The effective management of acute postoperative pain remains challenging, primarily owing to the short half-life and rapid systemic clearance of anesthetics. Therefore, this study aims to report structural characterization, pharmacokinetic profiling, and enhanced analgesic efficacy of a bioresponsive lyotropic liquid crystal Quject® gel for long-acting ropivacaine delivery. A lipid system of lecithin, Span 20, and tocopherol acetate, was systematically optimized via ternary phase diagram to identify formulations that transition from sol-to-gel upon contact with biological fluids. Structural characterization using SAXS and cryo-TEM confirmed the formation of a stable reversed hexagonal phase (lattice constant a≈5.80 nm; characteristic Bragg peaks at q≈0.80, 1.38, and 1.60 nm⁻1 with 1:√3:√4 ratio). The dense nanochannels of the hexagonal depot restricted ropivacaine diffusion, resulting in a minimal initial burst (Day-0: 3.80%) and 43.66% cumulative drug release by Day-7, compared to near-complete release (≥95%) from lamellar controls over the same period. In vivo pharmacokinetic analysis in rats revealed a 7-fold increase in elimination half-life (t1/2: 5.98vs. 0.81-h) and a 4-fold reduction in peak plasma concentration (Cmax: 58.13 vs. 231.00 ng/mL) compared to those of ropivacaine HCl, substantially mitigating systemic toxicity risk. The tlast concentration extended to 42-h, encompassing the critical 48-h postoperative recovery period. Furthermore, the von Frey test in a rat incision model confirmed sustained analgesic efficacy for up to 72-h after a single subcutaneous administration compared to ropivacaine HCl (≤6-h). These findings establish a direct structure-pharmacokinetics-efficacy relationship within Quject® gel, offering scalable, biocompatible prolonged postoperative analgesia.