An injectable in situ gel formed by ropivacaine with small lipid molecules to achieve long-term postoperative analgesia.

Summary

This preclinical study presents a stearic acid–ropivacaine hydrophobic ion-pair embedded in a glycerol monostearate in situ gel that provided multiday analgesia in mice while avoiding burst release. Histology and serum chemistry supported safety, suggesting a promising single-dose, long-acting local anesthetic platform for postoperative pain control.

Key Findings

• A ropivacaine–stearic acid hydrophobic ion-pair (SA-ROP HIP) combined with glycerol monostearate formed an in situ gel (SA-ROP-GMS) that avoided burst release.
• In mouse pain models, a single injection provided multiday (nearly 10-day) analgesia.
• Histology and blood biochemistry indicated no systemic toxicity with SA-ROP-GMS.
• All excipients were small molecules with favorable manufacturability and cost.

Clinical Implications

If translated to humans, this platform could enable single-shot, long-acting field blocks or wound infiltration, reducing opioid requirements, catheter use, and frequent redosing. Rigorous human PK/safety and local tissue compatibility studies are needed before clinical use.

Limitations

• Preclinical murine data; human pharmacokinetics, local tissue effects, and dose scaling remain unknown.
• Long-term local neurotoxicity and potential depot-related complications were not assessed.

Future Directions

Conduct GLP toxicology, large-animal nerve block studies, and first-in-human trials to define PK/PD, safety, and efficacy; compare with liposomal bupivacaine and catheter-based techniques.