Sustained Release from Ionic-Gradient Liposomes Significantly Decreases ETIDOCAINE Cytotoxicity

• Published in: Pharmaceutical research Vol. 35; no. 12; pp. 229 - 10
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2018; Springer; Springer Nature B.V
• Subjects: Ammonium sulfate; Analgesia; Analysis; Anesthetics; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cholesterol; Controlled release; Cytotoxicity; Electron paramagnetic resonance; Encapsulation; Etidocaine; Fibroblasts; Fluidity; High performance liquid chromatography; Kinetics; Lecithin; Light scattering; Liposomes; Liquid chromatography; Local anesthesia; Local anesthetics; Medical Law; Membrane fluidity; Nanoparticles; Pain perception; Pharmacology/Toxicology; Pharmacy; Photon correlation spectroscopy; Polydispersity; Research Paper; Resonance scattering; Sustained release; Transmission electron microscopy; Zeta potential; drug-delivery; local anesthesia; etidocaine; ionic gradient liposomes
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-018-2512-4

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 (NH 4 ) 2 SO 4 - 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 IGL EDC showed average diameters of 172.3 ± 2.6 nm, low PDI (0.12 ± 0.01), mean particle concentration of 6.3 ± 0.5 × 10 12 /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. IGL EDC can come to be a tool to reintroduce etidocaine in clinical use.