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

Author:

Cai Yuhao1,Li Qi1,Wesselmann Ursula2,Zhao Chao13ORCID

Affiliation:

1. Department of Chemical and Biological Engineering University of Alabama Tuscaloosa AL 35487 USA

2. Departments of Anesthesiology and Perioperative Medicine/Division of Pain Medicine Neurology and Psychology, and Consortium for Neuroengineering and Brain‐Computer Interfaces The University of Alabama at Birmingham Birmingham AL 35294 USA

3. Center for Convergent Biosciences and Medicine University of Alabama Tuscaloosa AL 35487 USA

Abstract

AbstractPeripherally injected local anesthetics exhibit limited ability to penetrate peripheral nerve barriers, which limits their effectiveness in peripheral nerve block and increases the risk of adverse effects. In this work, it is demonstrated that exosomes derived from Human Embryo Kidney 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, these exosomes are used 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‐h 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 h without causing systemic cardiotoxicity and local neurotoxicity and myotoxicity.

Funder

National Institute of Neurological Disorders and Stroke

Publisher

Wiley

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