Preparation and properties of arsonolipid containing liposomes

Arsonolipids are analogs of phosphonolipids which have a chemically versati le head group. In preliminary cell culture studies, liposomes composed sole ly of arsonolipids or of phosholipid-arsonolipid mixtures, demonstrate a sp ecific toxicity against cancer cells (Gortzi et al.. unpublished results). The possibility of using such formulations as an alternative of arsenic tri oxide with Or without combination of other cytostatic: agents: (encapsulate d in their aqueous interior) prompted the investigation of their physicoche mical characteristics. Herein we compared the: characteristics of arsonolip id containing vesicles with different lipid compositions. Experimental resu lts, and morphological observations reveal that non-sonicated formulations have different structures and stability (when both membrane integrity and a ggregation are taken into account) depending on the acyl chain length of th e arsonolipid. When phospholipids and especially cholesterol are included i n their membranes: almost all arsonolipids studied produce more stable vesi cles. An interesting aspect of these arsonolipid containing vesicles is als o their negative: surface charge, which may be modulated by mixing phosphol ipids with arsonolipids. Sonicated vehicles have smaller sizes and profound ly higher stability, especially when containing cholesterol and phosphatidy lcholine mixed with arsonolipids. The only exception is that of the arsonol ipid with the C-12 acyl chain which was observed to produce long tubes whic h break down to cubes by sonication. In conclusion, these initial studies d emonstrate that sonicated vesicles composed of arsonolipid and phospholipid mixtures mixed with cholesterol posses the stability required to be used a s an arsonolipid delivery system. In addition, although cryo-electron micro scopy demonstrated that the sonicated vesicles are elliptical in shape, the ir encapsulation efficiency is not significantly lower than sonicated phosp holipid liposomes. Thereby, these vesicles may be also used for the deliver y of other drug molecules which can be sufficiently retained in their aqueo us interior. (C) 2001 Published by Elsevier Science Ireland Ltd. All rights reserved.