Exosomal Bupivacaine: Integrating Nerve Barrier Penetration Capability and Sustained Drug Release for Enhanced Potency in Peripheral Nerve Block and Reduced Toxicity.

Summary

HEK293-derived exosomes were shown to cross the perineurium and were used to deliver bupivacaine, integrating barrier penetration with sustained release. The platform promises stronger, longer peripheral nerve block with reduced systemic toxicity compared with free bupivacaine.

Key Findings

• HEK293-derived exosomes effectively traversed the perineurium, the rate-limiting barrier for local anesthetics.
• Exosomes were used as carriers for bupivacaine, enabling sustained release at the nerve.
• The approach is designed to enhance block potency and reduce systemic toxicity versus free drug.

Clinical Implications

If translated, exosome-formulated local anesthetics could prolong block duration and reduce systemic toxicity, enabling lower doses and expanding ambulatory applications. Regulatory, manufacturing, and immunogenicity hurdles must be addressed before clinical use.

Limitations

• Preclinical study; absence of human safety and efficacy data
• Unresolved issues around scalable GMP manufacturing and immunogenicity of HEK293-derived exosomes

Future Directions

Evaluate pharmacokinetics, block duration, and neurotoxicity in large-animal models; optimize dosing; compare against liposomal bupivacaine; assess immunogenicity and manufacturability for clinical translation.