Behaviors of self-delivery lidocaine nano systems affected by intermolecular interaction

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.