An absorbable local anesthetic matrix provides several days of functional sciatic nerve blockade

Area of Science:

• Biomedical Engineering
• Pharmacology
• Neuroscience

Background:

• Local anesthesia aims for persistent peripheral nerve blockade for extended surgical procedures.
• Current local anesthetics offer limited duration (8-12 hours) post-injection.
• An implantable, controlled-release system using FDA-approved materials with lidocaine is developed for multi-day local delivery.

Purpose of the Study:

• To evaluate the efficacy and safety of Xybrex, a novel controlled-release lidocaine delivery system.
• To assess the duration of analgesia and motor block provided by Xybrex in a rat sciatic nerve model.
• To investigate potential local neurotoxicity and systemic toxicity associated with the Xybrex system.

Main Methods:

• Xybrex (16% lidocaine) was implanted adjacent to the sciatic nerve in rats at various doses.
• Analgesia and motor block were assessed behaviorally.
• Sciatic nerve neurotoxicity was evaluated histologically at multiple time points.
• In vitro lidocaine release kinetics from the matrix were measured.

Main Results:

• High-dose Xybrex provided complete analgesia for ~7 hours and partial analgesia for ~60 hours, significantly longer than lidocaine HCl solution.
• Complete motor block lasted ~17 hours, with full recovery observed within 15-24 days.
• Histological evaluation revealed minor inflammation similar to the control group, with no signs of systemic toxicity.
• In vitro release kinetics correlated with in vivo functional effects, indicating local drug interaction.

Conclusions:

• Xybrex is an effective, absorbable, controlled-release system for sustained peripheral nerve analgesia in rats.
• The system provides several days of pain relief without significant local neurotoxicity or systemic toxicity.
• Xybrex represents a promising advancement for long-lasting local anesthesia applications.