Title: Dibucaine in Ionic-Gradient Liposomes: Biophysical, Toxicological, and Activity Characterization
Author: Riske, Karin A.; Domingues, Cleyton C.; Casadei, Bruna R.; Mattei, Bruno; Caritá, Amanda C.; Lira, Rafael B.; Preté, Paulo S. C; De Paula, Eneida
Is part of: BIOPHYSICAL REVIEWS, v. 9, p. 649 - 667
Citation: Riske, Karin A.; Domingues, Cleyton C.; Casadei, Bruna R.; Mattei, Bruno; Caritá, Amanda C.; Lira, Rafael B.; Preté, Paulo S. C; De Paula, Eneida; Dibucaine in Ionic-Gradient Liposomes: Biophysical, Toxicological, and Activity Characterization. BIOPHYSICAL REVIEWS, v.9, p. 649-667, 2017
Abstract: Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 mM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of DBC. (c) 2018 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
Keywords: detergent resistant membranes; detergents; hemolysis; membrane; solubilization;
Subjects: CIENCIAS_BIOLOGICAS; Biofísica de Processos e Sistemas;
Funding: This workwas supported by Fapesp (#2013/13965-4 and #2014/14457-5) and Capes (V.M.C. fellowship).