In situ injectable lyotropic liquid crystal depot for sustained taphalgin release in acute postsurgical pain management

Acute postsurgical pain (APSP) poses significant pain management challenges in clinical due to limitations of current analgesics in efficacy or safety. This study developed an in situ injectable lyotropic liquid crystal (LLC) depot for sustained release of Taphalgin (TAP), a tetrapeptide agonist of μ 1 -opioid receptors with potent analgesia and low side effects. A TAP-loaded hexagonal phase liquid crystalline (TAP/EG-LLC-Gel) was constructed by the self-assembly of glyceryl monooleate (GMO) and egg yolk phosphatidylcholine (EYPC) via solvent exchange of propylene glycol with aqueous solution, characterized through polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), and rheological analysis. This TAP/EG-LLC-Gel demonstrated a cumulative release of 57.0 ± 2.6% (8 days) with mild initial burst release of 6.6 ± 1.8% (8 h), indicating favorable sustained release behaviors for TAP. Compared to free TAP, pharmacokinetic analysis revealed a 78-fold prolonged half-life (110.39 ± 30.10 h) for TAP/EG-LLC-Gel. The analgesic activity of TAP-LLC was evaluated in animal models of incision pain and acetic acid writhing, showing long-acting dose-dependent analgesia up to 8 days. This TAP-loaded in situ injectable LLC depot showed excellent sustained release behaviors with potent, long-acting and dose-dependent analgesia in two animal pain models, offering a promising solution for APSP management.