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

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Peripherally injected local anesthetics exhibit limited ability to penetrate peripheral nerve barriers (PNBs), which limits their effectiveness in peripheral nerve block and increases the risk of adverse effects. In this work, we demonstrated that exosomes derived from Human Embryo Kidney (HEK) 293 cells can effectively traverse the perineurium, which is the rate-limiting barrier within PNBs that local anesthetics need to cross before acting on axons. Based on this finding, we use these exosomes as a carrier for bupivacaine (BUP), a local anesthetic commonly used in clinical settings. The in vitro assessments revealed that the prepared exosomal bupivacaine (BUP@EXO) achieves a BUP loading capacity of up to 82.33% and sustained release of BUP for over 30 days. In rats, a single peripheral injection of BUP@EXO, containing 0.75 mg of BUP, which is ineffective for BUP alone, induced a 2-hour sensory nerve blockade without significant motor impairments. Increasing the BUP dose in BUP@EXO to 2.5 mg, a highly toxic dose for BUP alone, extended the sensory nerve blockade to 12 hours without causing systemic cardiotoxicity and local neurotoxicity and myotoxicity.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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