Effect of Charge on Separation of Liposomes upon Stagnation.

Abstract

Liposomes are used widely as drug delivery systems in different forms including nanosuspensions, osmotic pumps, infusion pumps, and IV injections. Some of these systems (e.g. infusion or osmotic pumps) might stay stagnant for a long time during or before administration, and therefore, might face phase separation. In spite of these, there are no data available about the behavior of liposomal systems upon stagnation in such drug delivery systems. As a part of a series of investigations on convective flow and stagnation of liposomes, the current work represents the effects of charge on liposomes separation upon stagnation. Positive, negative, and neutral liposomes, with zeta potentials of +56, -50 and 1.4 mV respectively, were prepared and encountered gravity (separating force) in a designed sedimentation model. Samples were collected over 25 h and their D0.5 (diameter which half of the particles are smaller than), particle size distribution, and phospholipid contents were evaluated. The ratio of the D0.5 in the last to the first sample, (Separation Factor) for positive, negative, and neutral liposomes were calculated to be 1.00 (no separation), 0.98 (no separation), and 0.33 (separation) respectively. The same trend was observed for lipid contents and particles population. These data show that liposomes' charge affect their separation under gravity and is a very important factor in their uniformity upon storage, pre-administrational steps, and even during administration in systems such as infusion pumps.