Indocyanine green-mediated photothermal release of lidocaine from genipin-crosslinked gelatin hydrogel in nerve block

Local anesthetic (LA)-induced peripheral nerve block (PNB) is an important part of multimodal analgesia to reduce postoperative pain, accelerate postoperative recovery, and improve clinical prognosis. The duration of LA depends on anesthetics, and the repeated nerve positioning, puncture injection or indwelling catheter is often required to prolong the effect of PNB. In this study, the genipin, was used to crosslink gelatin-based hydrogel, and then co-loaded with indocyanine green (ICG) and lidocaine as an LA-controlled release system (ICG@Lido/Gel and ICG@Lido/gGel). The viscosity of the genipin-crosslinked gelatin hydrogel (gGel) could be controlled by the genipin/gelatin ratio to achieve the slow release of lidocaine. The ICG@Lido/Gel and ICG@Lido/gGel were biocompatible, and could reduce the instant concentration of lidocaine to minimize its direct cytotoxicity. The ICG@Lido/Gel and ICG@Lido/gGel could increase the PNB period to 70.8 min and 77.8 min, respectively. After NIR exposure, the PNB was introduced again and sustained to 20.8 min for ICG@Lido/Gel and 31.7 min for ICG@Lido/gGel. Therefore, the ICG@Lido/gGel could significantly prolong the PNB duration via increasing the residence time of lidocaine at the injection site, slowing the lidocaine release, and triggering the lidocaine release by NIR exposure. The ICG@Lido/gGel may expresses potential as a photothermal-triggered release system for PNB.