Sustained Release from Ionic-Gradient Liposomes Significantly Decreases ETIDOCAINE Cytotoxicity

Autor(es)

Oliveira, Juliana Damasceno ^[1] ; de Morais Ribeiro, Ligia Nunes ^[1] ; Rodrigues da Silva, Gustavo Henrique ^[1] ; Casadei, Bruna Renata ^[2] ; Couto, Veronica Muniz ^[1] ; Martinez, Elizabeth Ferreira ^[3] ; de Paula, Eneida ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas Unicamp, Dept Biochem & Tissue Biol, Inst Biol, POB 6109, BR-13083862 Campinas, SP - Brazil

^[2] Fed Univ Sao Paulo UNIFESP, Dept Biophys, Sao Paulo, SP - Brazil

^[3] Sao Leopoldo Mand Inst & Res Ctr, Dept Oral Pathol, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICAL RESEARCH; v. 35, n. 12 DEC 2018.
• Citações Web of Science: 2

Resumo

PurposeEtidocaine (EDC) is a long lasting local anesthetic, which alleged toxicity has restricted its clinical use. Liposomes can prolong the analgesia time and reduce the toxicity of local anesthetics. Ionic gradient liposomes (IGL) have been proposed to increase the upload and prolong the drug release, from liposomes.MethodsFirst, a HPLC method for EDC quantification was validated. Then, large unilamellar vesicles composed of hydrogenatedsoy phosphatidylcholine:cholesterol with 250mM (NH4)(2)SO4 - inside gradient - were prepared for the encapsulation of 0.5% EDC. Dynamic light scattering, nanotracking analysis, transmission electron microscopy and electron paramagnetic resonance were used to characterize: nanoparticles size, polydispersity, zeta potential, concentration, morphology and membrane fluidity. Release kinetics and in vitro cytotoxicity tests were also performed.ResultsIGL(EDC) showed average diameters of 172.32.6nm, low PDI (0.12 +/- 0.01), mean particle concentration of 6.3 +/- 0.5x10(12)/mL and negative zeta values (-10.2 +/- 0.4mV); parameters that remain stable during storage at 4 degrees C. The formulation, with 40% encapsulation efficiency, induced the sustained release of EDC (ca. 24h), while reducing its toxicity to human fibroblasts.Conclusion A novel formulation is proposed for etidocaine that promotes sustained release and reduces its cytotoxicity. IGL(EDC) can come to be a tool to reintroduce etidocaine in clinical use. (AU)

• Processo FAPESP: 14/14457-5 - Carreadores baseados em lipídios (SLN/NLC e lipossomas com gradiente iônico) como estratégia para aumentar a encapsulação e a potência de anestésicos locais
• Beneficiário: Eneida de Paula
• Modalidade de apoio: Auxílio à Pesquisa - Temático