A trick of the light: Novel technologies for sizing liposomal drug-delivery particles

two light-scattering techniques often have complementary roles. SLS or MALS measures the timeaveraged intensity of scattered light from the molecules in solution at one or a plurality of angles. The intensity is proportional to the concentration and molecular mass of the molecule in the solution (Figure 1). MALS detectors, in particular, are widely used in measuring the absolute molecular mass of proteins and other polymers independent of the shape of the molecules. The angular dependence of the scattered light yields the size of the molecule, known as the RMS (root mean square) radius. MALS measurements can be carried out either in a stand-alone ‘batch’ mode or, more often, in conjunction with a separation technique [SEC (size-exclusion chromatography) or FFF (field flow fractionation)]. In contrast with MALS, DLS analyses the rapid time-intensity fluctuations in the scattered light, due to the Brownian motion of the molecules in solution, to determine a molecule’s size. The rate of the timeintensity changes is directly related to the translational diffusion of the particles, from which the hydrodynamic size and size distribution of the molecules is determined (Figure 2). DLS size distributions provide information about the homogeneity Because of their relatively high carrying capacity, lower toxicity and protection against dilution, liposomes are excellent carriers of therapeutic biological molecules such as antibodies, peptides and proteins. Liposomes also offer a protective environment for drug compounds, encasing watersoluble drugs in an aqueous pouch. One of the most important physical characteristics of these drug-delivery nanoparticles is their size and size distribution, physical characteristics affecting the stability and efficacy of the encapsulated drug2. The determination of the size and uniformity of the liposome has classically been performed by a host of techniques, including electron microscopy, fluorescent microscopy and HPLC. Recently, novel light-scattering technologies have become available and their application to liposome characterization is discussed in detail in the present article. Two types of light-scattering technologies, SLS [static light scattering; also known as classical MALS (multi-angle light scattering)] and DLS (dynamic light scattering; also known as quasi-elastic light scattering), have been applied extensively to biomolecular characterization. These of the molecules quickly and without perturbing the sample3. Typically DLS is performed manually in batch experiments using high-quality quartz cells, although recently DLS plate readers, using disposable or quartz microplates, have become available for high-throughput DLS experiments. DLS plate reader systems increase productivity by a factor of ten or more over conventional batch DLS systems.