1. Academic Validation
  2. Sustained Release from Ionic-Gradient Liposomes Significantly Decreases ETIDOCAINE Cytotoxicity

Sustained Release from Ionic-Gradient Liposomes Significantly Decreases ETIDOCAINE Cytotoxicity

  • Pharm Res. 2018 Oct 10;35(12):229. doi: 10.1007/s11095-018-2512-4.
Juliana Damasceno Oliveira 1 Lígia Nunes de Morais Ribeiro 1 Gustavo Henrique Rodrigues da Silva 1 Bruna Renata Casadei 2 Verônica Muniz Couto 1 Elizabeth Ferreira Martinez 3 Eneida de Paula 4
Affiliations

Affiliations

  • 1 Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas - Unicamp, P.O. Box - 6109, CEP, Campinas, SP, 13083-862, Brazil.
  • 2 Department of Biophysics, Federal University of São Paulo - UNIFESP, São Paulo, São Paulo, Brazil.
  • 3 Department of Oral Pathology, São Leopoldo Mandic Institute and Research Center, Campinas, São Paulo, Brazil.
  • 4 Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas - Unicamp, P.O. Box - 6109, CEP, Campinas, SP, 13083-862, Brazil. depaula@unicamp.br.
Abstract

Purpose: Etidocaine (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.

Methods: First, a HPLC method for EDC quantification was validated. Then, large unilamellar vesicles composed of hydrogenated soy phosphatidylcholine:cholesterol with 250 mM (NH4)2SO4 - 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.

Results: IGLEDC showed average diameters of 172.3 ± 2.6 nm, low PDI (0.12 ± 0.01), mean particle concentration of 6.3 ± 0.5 × 1012/mL and negative zeta values (-10.2 ± 0.4 mV); parameters that remain stable during storage at 4°C. The formulation, with 40% encapsulation efficiency, induced the sustained release of EDC (CA. 24 h), while reducing its toxicity to human fibroblasts.

Conclusion: A novel formulation is proposed for etidocaine that promotes sustained release and reduces its cytotoxicity. IGLEDC can come to be a tool to reintroduce etidocaine in clinical use.

Keywords

drug-delivery; etidocaine; ionic gradient liposomes; local anesthesia.

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