Study of the influence of ascorbyl palmitate and amiodarone in the stability of unilamellar liposomes

LUCIANO A. BENEDINI; SILVIA S. ANTOLLINI; MARIA LAURA FANANI; SANTIAGO PALMA; PAULA MESSINA; PABLO SCHULZ

MOLECULAR MEMBRANE BIOLOGY

TAYLOR & FRANCIS LTD

Lugar: Londres; Año: 2014 vol. 31 p. 85 - 94

0968-7688

Amiodarone (AMI) is a low water-solubility drug, which is very useful in treatment of severe cardiac disease. Its adverse effects are associated with toxicity in different tissues. Lysosomal phospholipidosis is a potential mechanism of AMI toxicity. Several antioxidants have been shown to reduce, and prevent AMI toxicity. The aim of this work is to develop and characterize Dimyristoyl phosphatidylcholine (DMPC) liposomal carriers doped with the antioxidant ascorbyl palmitate (Asc16), in order to either minimize or avoid the adverse effects produced by AMI. The employment of liposomes would avoid the use of cosolvents in AMI formulations, and Asc16 minimizes the adverse effects of AMI. To evaluate the partition and integration of AMI and Asc16 in lipid membranes, penetration studies onto DMPC monolayers were carried out. Both AMI and Asc16 showed surface activity, affecting the surface tension of the air/water interface and reaching surface pressures of 30-35 mN/m. When a phospholipid monolayer was placed at the interface both drugs showed a greater penetration to the monolayer than to bare air/water interface being Asc16 more potent than AMI (interaction pressures of 19mN/m for Asc16 and 8mN/m for AMI), evidencing a favorable partition to the membrane phase. The presence of 20mol% of Asc16 in the monolayer did not affect significatively the interaction of AMI with the phospholipid monolayer. The disturbance of the liposomes membranes was studied by generalized polarization (GP). The stability of liposomes was evaluated by the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Experimentally determined size particle and zeta potential (ζ) were used to apply DLVO theory. The obtained liposomes were stable in the experimental conditions and kept their size uniform (~ 160 nm) with increasing concentrations of AMI and Asc16 indicating that such systems are suitable for amiodarone delivery function.