Abstract
Lidocaine salts self-assembled into different nano systems in water at a clinical dosage (2%, 0.2 mL) without excipient addition, and led to different sensory block durations and acute systemic toxicities, which were affected by the self-delivery and self-release behaviors of the salts in vivo. These differences were mainly caused by intermolecular π-π stacking under different conditions, which was proved by the unique supramolecular arrangement of gourd-shaped Janus particles. π-π stacking in lidocaine nano systems can be enhanced by carbon dioxide addition or the exchange of counter ions from Br- to Cl-. Without π-π stacking, nano systems self-assembled by lidocaine hydrobromide achieved 7.8 h sensory block by intradermal administration on rats, which is much longer than the efficacy of classical local anesthetics and more suitable for postoperative treatment.
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