doi:10.1016/j.biomaterials.2022.121453engPrieto, MartinUsón, LauraGarcía-Salinas, SaraYus, CristinaLanda, GuillermoAlejo, TeresaLujan, LluisPérez, MartaIrusta, SilviaSebastian, VictorMendoza, GraciaArruebo, ManuelLight activated pulsatile drug delivery for prolonged peripheral nerve blockART-2022-128455Regional anesthesia is widely used in peripheral nerve block and in neuraxial anesthesia to reduce anesthetics systemic side effects and shorten recovery times. However, when applied as a single injection (e.g., peripheral nerve block) it is limited by the duration of its effect. Herein, we develop a thermoresponsive nanogel based on poly(oligoethylene glycol methacrylate) containing the long-lasting anesthetic bupivacaine, which can be externally activated by using near-infrared light due to the photothermal properties of hollow gold nanoparticles embedded in the nanogel which facilitate its phase transition, triggering drug release at a controlled temperature above body temperature. Bupivacaine in vitro release can be repeatedly triggered to achieve a controlled pulsatile release of the drug due to the reversible nature of the thermosensitive nanogel, achieving a spatio-temporal control of the release. In vivo sciatic nerve block demonstrates that whereas the administered dose of free bupivacaine produces sensory block and impaired motor function for 2 h, the equivalent bupivacaine dose included in the developed release system can significantly prolong its neurobehavioral anesthetic effect for over 6 h. This release system can also be reactivated multiple times by subsequent irradiation cycles without observing detrimental toxicity in the infiltrated tissues. © 2022 Elsevier Ltd2022http://zaguan.unizar.es/record/16303610.1016/j.biomaterials.2022.121453http://zaguan.unizar.es/record/163036oai:zaguan.unizar.es:163036info:eu-repo/grantAgreement/EUR/ERC-2013-CoG-614715info:eu-repo/grantAgreement/ES/ISCIII/MS19-00092info:eu-repo/grantAgreement/ES/MCINN/PRE2018-085769info:eu-repo/grantAgreement/ES/MICINN BES-2015-073735Biomaterials 283 (2022), 121453 [16 pp.]by-nc-ndhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.esinfo:eu-repo/semantics/openAccess