Portal de Periódicos da CAPES

Artigo Produção Nacional Revisado por pares

BIBTEX RIS

DoE development of ionic gradient liposomes: A successful approach to improve encapsulation, prolong anesthesia and decrease the toxicity of etidocaine

2023; Elsevier BV; Volume: 634; Linguagem: Inglês

10.1016/j.ijpharm.2023.122672

1873-3476

Juliana Damasceno Oliveira, Gustavo H. Rodrigues da Silva, Ludmila David de Moura, Gabriela Göethel, Juliana Zampoli Boava Papini, Bruna Renata Casadei, Lígia Nunes de Morais Ribeiro, Luís Fernando Cabeça, Solange Cristina García, Elizabeth Ferreira Martinez, Giovana Radomille Tófoli, Eneida de Paula,

Nanoparticle-Based Drug Delivery

Etidocaine (EDC) is a long-acting local anesthetic of the aminoamide family whose use was discontinued in 2008 for alleged toxicity issues. Ionic gradient liposomes (IGL) are nanostructured carriers for which an inner/outer gradient of ions increases drug upload. This work describes IGLEDC, a formulation optimized by Design of Experiments, composed of hydrogenated soy phosphatidylcholine:cholesterol:EDC, and characterized by DLS, NTA, TEM/Cryo-TEM, DSC and 1H NMR. The optimized IGL showed significant encapsulation efficiency (41 %), good shelf stability (180 days) and evidence of EDC interaction with the lipid bilayer (as seen by DSC and 1H NMR results) that confirms its membrane permeation. In vitro (release kinetics and cytotoxicity) tests showed that the encapsulation of EDC into the IGL promoted sustained release for 24 h and decreased by 50 % the intrinsic toxicity of EDC to Schwann cells. In vivo IGLEDC decreased the toxicity of EDC to Caenorhabditis elegans by 25 % and extended its anesthetic effect by one hour, after infiltrative administration, at clinically used (0.5 %) concentration, in rats. Thus, this novel drug delivery system is a promise for the possible reintroduction of EDC in clinics, aiming at the control of operative and postoperative pain.