Title: Sustained Release from Ionic-Gradient Liposomes Significantly Decreases ETIDOCAINE Cytotoxicity
Author: Oliveira, Juliana Damasceno; Ribeiro, Lígia Nunes De Morais; Rodrigues Da Silva, Gustavo Henrique; Casadei, Bruna Renata; Couto, Verônica Muniz; Martinez, Elizabeth Ferreira; De Paula, Eneida
Is part of: PHARMACEUTICAL RESEARCH, v. 35, p. 229 -
Citation: Oliveira, Juliana Damasceno; Ribeiro, Lígia Nunes De Morais; Rodrigues Da Silva, Gustavo Henrique; Casadei, Bruna Renata; Couto, Verônica Muniz; Martinez, Elizabeth Ferreira; De Paula, Eneida; Sustained Release from Ionic-Gradient Liposomes Significantly Decreases ETIDOCAINE Cytotoxicity. PHARMACEUTICAL RESEARCH, v.35, p. 229-, 2018
Abstract: 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.
Keywords: drug delivery systems; etidocaine; ionic gradient liposomes;
Subjects: CIENCIAS_BIOLOGICAS; Biofísica de Processos e Sistemas; CIENCIAS_BIOLOGICAS; Farmacologia; Farmacologia Bioquímica e Molecular;
Funding: The authors acknowledge Fapesp (# 2014/14457-5), and CNPq (J.D.O. and E.P fellowships) for financial support. They are also grateful to Dr. Maria Teresa Lamy for the access to the EPR facility.