| Autor: |
Souza AD; Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas (Unicamp), ZIP 13083-862 Campinas, São Paulo, Brazil., Rodrigues da Silva GH; Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas (Unicamp), ZIP 13083-862 Campinas, São Paulo, Brazil.; Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, ZIP 13083-100 Campinas, São Paulo, Brazil., Ribeiro LNM; Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas (Unicamp), ZIP 13083-862 Campinas, São Paulo, Brazil., Mitsutake H; Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas (Unicamp), ZIP 13083-862 Campinas, São Paulo, Brazil.; Niels Bohr Institute, University of Copenhagen, ZIP 2100 Copenhagen, Denmark., Bordallo HN; Niels Bohr Institute, University of Copenhagen, ZIP 2100 Copenhagen, Denmark., Breitkreitz MC; Departamento de Química Analítica, Instituto de Química, Unicamp, ZIP 13083-862 Campinas, São Paulo, Brazil., Lima Fernandes PC; Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas (Unicamp), ZIP 13083-862 Campinas, São Paulo, Brazil., Moura LD; Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas (Unicamp), ZIP 13083-862 Campinas, São Paulo, Brazil., Yokaichiya F; Departamento de Física, Universidade Federal do Paraná (UFPR), ZIP 81531-980 Curitiba, Paraná, Brazil., Franco M; Instituto de Pesquisas Energéticas e Nucleares, IPEN-CNEN/SP, ZIP 05508-000 São Paulo, São Paulo, Brazil., de Paula E; Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas (Unicamp), ZIP 13083-862 Campinas, São Paulo, Brazil. |
| Abstrakt: |
Nanostructured lipid carriers (NLC) have emerged as innovative drug delivery systems, offering distinct advantages over other lipid-based carriers, such as liposomes and solid lipid nanoparticles. Benzocaine (BZC), the oldest topical local anesthetic in use, undergoes metabolism by pseudocholinesterase, leading to the formation of p -aminobenzoic acid, a causative agent for allergic reactions associated with prolonged BZC usage. In order to mitigate adverse effects and enhance bioavailability, BZC was encapsulated within NLC. Utilizing a 2 3 factorial design, formulations comprising cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid), and Pluronic F68 as surfactants were systematically prepared, with variations in the solid/liquid lipid mass ratios (60:40-80:20%), total lipid contents (15-25%), and BZC concentrations (1-3%). The optimized formulation underwent characterization by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis, and transmission electron microscopy (TEM)/cryo-TEM, providing insights into the nanoparticle structure and the incorporation of BZC into its lipid matrix. NLC BZC exhibited a noteworthy encapsulation efficiency (%EE = 96%) and a 1 year stability when stored at 25 °C. In vitro kinetic studies and in vivo antinociceptive tests conducted in mice revealed that NLC BZC effectively sustained drug release for over 20 h and prolonged the anesthetic effect of BZC for up to 18 h. We therefore propose the use of NLC BZC to diminish the effective anesthetic concentration of benzocaine (from 20 to 3% or less), thus minimizing allergic reactions that follow the topical administration of this anesthetic and, potentially, paving the way for new routes of BZC administration in pain management. |
