Long-term sciatic nerve block led by a supramolecular arrangement of self-delivery local anesthetic nano systems.

Classical local anesthetics are unsuitable to treat regional pain lasting several days due to their limited duration and systemic toxicity. Self-delivery nano systems without excipients were designed for long-term sensory blocks. 1a self-assembled into different vehicles with different fractions of intermolecular π-π stacking, transported itself into nerve cells, and released single molecules slowly to achieve long-term duration for rats' sciatic nerve block for 11.6 h in water, 12.1 h in water with CO2 and 3.4 h in NS (normal saline). After the counter ions were changed to SO42-, 1e can self-assemble into vesicles and prolong the duration to 43.2 h, which was much longer than the 3.8 h led by (s)-bupivacaine hydrocloride (0.75%). This was mainly caused by the enhancement of self-release and counter ion exchange inside nerve cells, which were affected by the gemini surfactant structure, pKa of the counter ions and π-π stacking interactions.

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

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.

Switchable Nanostructures Triggered by Noyori-Type Organometallics.

Janus particles (JPs) self-assembled by a typical small organic gemini surfactant in water were reported by us. After the addition of a small amount Noyori-type organometallics to an organic solvent, these gourd-shaped JPs became new nanostructures, such as nanotubes (NTs), nanoribbons (NRs), and new types of JPs. Significant changes in specific rotation occurred on the solution-like samples, triggered by chiral organometallics in 20 µL of ethyl acetate. Almost all of these organometallics-triggered nanostructures can be conveniently detached and reversed within 5 min due to the easy-phase separation of ethyl acetate from the emulsion and the chemical-selective unstable binding between the organometallics and carbonate group on the surfactant.