Dibucaine in ionic-gradient liposomes: biophysical, toxicological and activity characterisation

VERONICA M. COUTO; MARIA J. PRIETO; DANIELA E. IGARTÚA; DANIELA A. FEAS; LÍGIA N.M. RIBEIRO; CAMILA M.G. SILVA; SIMONE R. CASTRO; VIVIANE A. GUILHERME; DARLENE D. DANTZGER; DAISY MACHADO; SILVIA DEL V. ALONSO; ENEIDA DE PAULA

JOURNAL OF PHARMACEUTICAL SCIENCES

JOHN WILEY & SONS INC

Lugar: New York; Año: 2018

0022-3549

Administration of local anaesthetics (LA) is one of the most effective pain control techniques forpostoperative analgesia. However, anaesthetic agents easily diffuse into the injection site, limitingthe time of anaesthesia. One approach to prolong analgesia is to entrap LA in nanostructuredcarriers (e.g. liposomes). Here we report that using an ammonium sulphate gradient was the beststrategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scatteringand nanotracking analyses were used to characterise vesicle properties, such as, size,polydispersity, zeta potentials and number. In vitro kinetic experiments revealed the sustainedrelease of DBC (50% in 7 h) from the liposomes. Additionally, in vitro (3T3 cells in culture) and invivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBCcyto/cardiotoxicity, as well as morphological changes in zebrafish larvae. Moreover, the anaesthesiatime attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) thanwith free DBC (11 h), at 320 µM (0.012%), confirming it as a promising long-acting liposomeformulation for parenteral drug administration of dibucaine.