Lipid nanoparticles loaded with butamben and designed to improve anesthesia at inflamed tissues dagger

Autor(es):Mostrar menos -

Rodrigues da Silva, Gustavo H. ^[1] ; Paes Lemes, Julia Borges ^[2] ; Geronimo, Gabriela ^[1] ; de Lima, Fernando Freitas ^[1] ; de Moura, Ludmilla David ^[1] ; dos Santos, Ariany Carvalho ^[3] ; Carvalho, Nathalia Santos ^[2] ; Malange, Kaue Franco ^[2] ; Breitkreitz, Marcia C. ^[4] ; Parada, Carlos A. ^[2] ; de Paula, Eneida ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Dept Struct & Funct Biol, Inst Biol, Campinas, SP - Brazil

^[3] Fed Univ Grande Dourados, Fac Hlth Sci, Dourados, MS - Brazil

^[4] Univ Estadual Campinas, Dept Analyt Chem, Inst Chem, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOMATERIALS SCIENCE; v. 9, n. 9, p. 3378-3389, MAY 7 2021.
• Citações Web of Science: 1

Resumo

The most frequently used local anesthetics (LA) for local infiltration have an ionizable amine in the range of pH 7.6-8.9. Effective anesthesia of inflamed tissues is a great challenge, especially because the induced local acidosis decreases the fraction of the neutral (more potent) LA species in situ. To solve this limitation, the butyl-substituted benzocaine analogue butamben (BTB) - that has no ionizable amine group close to the physiological pH - could be useful if it was not for its low solubility. To overcome the solubility problem, an optimized formulation for BTB using nanostructured lipid carriers (NLC) was developed by a factorial design and characterized using DLS, XRD, DSC and cryo-EM. The release kinetics and cytotoxicity of the new formulation were measured in vitro, while the in vivo tests assessed its effectiveness on healthy and inflamed tissues, in rats. The optimized NLCBTB formulation showed desirable physicochemical properties (size = 235.6 +/- 3.9 nm, polydispersity = 0.182 +/- 0.006 and zeta potential = -23.6 +/- 0.5 mV), high (99.5%) encapsulation efficiency and stability during 360 days of storage at room temperature. NLCBTB prolonged the release of butamben and decreased its in vitro cytotoxicity without inducing any in vivo toxic alteration. In the inflammatory hyperalgesia model, the NLCBTB formulation showed potential for the management of inflammatory pain, displaying greater analgesic effectiveness (40%) and a prolonged effect. (AU)

• Processo FAPESP: 17/15174-5 - Desenvolvimento de nanopartículas lipídicas funcionais para o aumento da potência anestésica em tecidos inflamados
• Beneficiário: Gustavo Henrique Rodrigues da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/25372-0 - Desenvolvimento de carreadores lipídicos nanoestruturados para encapsulação de anestésicos locais processados em matrizes biopoliméricas para aplicação tópica em mucosa oral
• Beneficiário: Lígia Nunes de Morais Ribeiro
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado