000119777 001__ 119777
000119777 005__ 20230519145410.0
000119777 0247_ $$2doi$$a10.1021/acsami.1c00894
000119777 0248_ $$2sideral$$a124897
000119777 037__ $$aART-2021-124897
000119777 041__ $$aeng
000119777 100__ $$0(orcid)0000-0002-9324-0446$$aAlejo, Teresa$$uUniversidad de Zaragoza
000119777 245__ $$aNanogels with High Loading of Anesthetic Nanocrystals for Extended Duration of Sciatic Nerve Block
000119777 260__ $$c2021
000119777 5060_ $$aAccess copy available to the general public$$fUnrestricted
000119777 5203_ $$aThe development of thermoresponsive nanogels loaded with nanocrystals of the local anesthetic bupivacaine nanocrystals (BNCs) for prolonged peripheral nerve pain relief is reported here. BNCs were prepared using the antisolvent
precipitation method from the hydrophobic form of bupivacaine(bupivacaine free base). The as-prepared BNCs were used stand-alone or encapsulated in temperature-responsive poly(ethylene glycol) methyl ether methacrylate (OEGMA)-based nanogels, resulting in bupivacaine NC-loaded nanogels (BNC-nanogels) of monodisperse size. The synthesis protocol has rendered high drug loadings (i.e., 93.8 ±1.5 and 84.8 ±1.2 wt % for the NC and BNC-nanogels, respectively) and fast drug dissolution kinetics in the resulting composite material. In vivo tests demonstrated the efficacy of the formulation along with an extended duration of sciatic nerve block in murine models of more than 8 h with a formulation containing only 2 mg of the local anesthetic thanks to the thermoresponsive character of the polymer, which, at body temperature, becomes hydrophobic and acts as a diffusion barrier for the encapsulated drug nanocrystals. The hydrophobicity of the encapsulated bupivacaine free base probably facilitates its pass through cell membranes and also binds strongly to their hydrophobic lipid bilayer, thereby protecting molecules from diffusion to extracellular media and to the bloodstream, reducing their clearance. When using BNC-nanogels, the duration of the anesthetic blockage lasted twice as long as compared to the effect of just BNCs or a conventional bupivacaine hydrochloride solution both containing equivalent amounts of the free drug. Results of the in vivo tests showed enough sensory nerve block to potentially relieve pain, but still having mobility in the limb, which enables motor function when required. The BNC-nanogels presented minimal toxicity in the in vivo study due to their sustained drug release and excellent biocompatibility. The encapsulation of nano-sized crystals of bupivacaine provides a prolonged regional anesthesia with reduced toxicity, which could be advantageous in the management of chronic pain.
000119777 536__ $$9info:eu-repo/grantAgreement/EUR/ERC-2013-CoG-614715$$9info:eu-repo/grantAgreement/ES/MCIU/RTI2018-099019-A-I00
000119777 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000119777 590__ $$a10.383$$b2021
000119777 591__ $$aMATERIALS SCIENCE, MULTIDISCIPLINARY$$b49 / 345 = 0.142$$c2021$$dQ1$$eT1
000119777 591__ $$aNANOSCIENCE & NANOTECHNOLOGY$$b23 / 109 = 0.211$$c2021$$dQ1$$eT1
000119777 592__ $$a2.143$$b2021
000119777 593__ $$aMedicine (miscellaneous)$$c2021$$dQ1
000119777 593__ $$aMaterials Science (miscellaneous)$$c2021$$dQ1
000119777 594__ $$a14.4$$b2021
000119777 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000119777 700__ $$0(orcid)0000-0002-4678-7465$$aUson, Laura$$uUniversidad de Zaragoza
000119777 700__ $$0(orcid)0000-0003-1599-8216$$aLanda, Guillermo$$uUniversidad de Zaragoza
000119777 700__ $$0(orcid)0000-0002-2576-6382$$aPrieto, Martin
000119777 700__ $$0(orcid)0000-0002-1505-498X$$aYus Argón, Cristina$$uUniversidad de Zaragoza
000119777 700__ $$0(orcid)0000-0002-0595-5514$$aGarcia-Salinas, Sara
000119777 700__ $$ade Miguel, Ricardo$$uUniversidad de Zaragoza
000119777 700__ $$0(orcid)0000-0002-2685-1730$$aRodríguez-Largo, Ana$$uUniversidad de Zaragoza
000119777 700__ $$0(orcid)0000-0002-2966-9088$$aIrusta, Silvia$$uUniversidad de Zaragoza
000119777 700__ $$0(orcid)0000-0002-6873-5244$$aSebastian, Victor$$uUniversidad de Zaragoza
000119777 700__ $$aMendoza, Gracia
000119777 700__ $$0(orcid)0000-0003-3165-0156$$aArruebo, Manuel$$uUniversidad de Zaragoza
000119777 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000119777 7102_ $$15005$$2555$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Ingeniería Química
000119777 7102_ $$15005$$2790$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Tecnologi. Medio Ambiente
000119777 773__ $$g13, 15 (2021), 17220-17235$$pACS appl. mater. interfaces$$tACS applied materials & interfaces$$x1944-8244
000119777 8564_ $$s9625581$$uhttps://zaguan.unizar.es/record/119777/files/texto_completo.pdf$$yVersión publicada
000119777 8564_ $$s3380810$$uhttps://zaguan.unizar.es/record/119777/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000119777 909CO $$ooai:zaguan.unizar.es:119777$$particulos$$pdriver
000119777 951__ $$a2023-05-18-13:54:10
000119777 980__ $$aARTICLE