Particle Sizing of Liposomal Dispersions: A Critical Evaluation of Some Quasi-Elastic Light-Scattering Data-Analysis Software Programs

Abstract

The particle size of four liposomal dispersions was estimated by quasi-elastic light scattering. The data were analyzed by three different software programs. Comparing the estimated values for the average particle size and the particle size distribution, some differences became obvious. First, it was observed that the average values obtained by different calculation methods were hardly comparable, since some systematic deviations occurred. Comparing the estimated particle size distributions, the Malvern Automeasure software was shown to produce overly smoothed, broad monomodal distributions. On the other hand, the results of both the CONTIN and the Brookhaven ISDA package agreed much better with the particle size distributions estimated by image analysis of electron microscopic photographs, revealing that all samples studied were bimodal, containing small liposomes with a rather constant diameter as well as much bigger aggregates that were gradually broken down during sonication. Concerning the ISDA software in detail, more accurate results were obtained by the NNLS-based histogram method compared to the exponential sampling method. Overall, CONTIN seemed to yield the most reliable distributions, since the smaller liposomes were detected even in the unsonicated sample.