119777 20230519145410.0 doi 10.1021/acsami.1c00894 sideral 124897 ART-2021-124897 eng Alejo, Teresa Universidad de Zaragoza (orcid)0000-0002-9324-0446 Nanogels with High Loading of Anesthetic Nanocrystals for Extended Duration of Sciatic Nerve Block 2021 Access copy available to the general public Unrestricted The 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. info:eu-repo/grantAgreement/EUR/ERC-2013-CoG-614715 info:eu-repo/grantAgreement/ES/MCIU/RTI2018-099019-A-I00 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 10.383 2021 MATERIALS SCIENCE, MULTIDISCIPLINARY 49 / 345 = 0.142 2021 Q1 T1 NANOSCIENCE & NANOTECHNOLOGY 23 / 109 = 0.211 2021 Q1 T1 2.143 2021 Medicine (miscellaneous) 2021 Q1 Materials Science (miscellaneous) 2021 Q1 14.4 2021 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Uson, Laura Universidad de Zaragoza (orcid)0000-0002-4678-7465 Landa, Guillermo Universidad de Zaragoza (orcid)0000-0003-1599-8216 Prieto, Martin (orcid)0000-0002-2576-6382 Yus Argón, Cristina Universidad de Zaragoza (orcid)0000-0002-1505-498X Garcia-Salinas, Sara (orcid)0000-0002-0595-5514 de Miguel, Ricardo Universidad de Zaragoza Rodríguez-Largo, Ana Universidad de Zaragoza (orcid)0000-0002-2685-1730 Irusta, Silvia Universidad de Zaragoza (orcid)0000-0002-2966-9088 Sebastian, Victor Universidad de Zaragoza (orcid)0000-0002-6873-5244 Mendoza, Gracia Arruebo, Manuel Universidad de Zaragoza (orcid)0000-0003-3165-0156 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 5005 555 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Ingeniería Química 5005 790 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Tecnologi. Medio Ambiente 13, 15 (2021), 17220-17235 ACS appl. mater. interfaces ACS applied materials & interfaces 1944-8244 9625581 http://zaguan.unizar.es/record/119777/files/texto_completo.pdf Versión publicada 3380810 http://zaguan.unizar.es/record/119777/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:119777 articulos driver 2023-05-18-13:54:10 ARTICLE