Practical aspects in size and morphology characterization of drug-loaded nano-liposomes

In this study, we compare two most commonly used approaches for assessing the size distribution and morphology of liposomal nano-drug systems, namely, dynamic light scattering (DLS) and cryogenic-transmission electron microscopy (cryo-TEM); an automated quantitative analysis method was developed for the latter method. We demonstrate the advantages and disadvantages of each of these two approaches for a commercial formulation of the anti-cancer drug doxorubicin - Doxil®, in which the drug is encapsulated, mostly in the form of nano-rod crystals. With increasing drug concentration, these nano-rods change the shape of the liposomes from spherical, before drug loading, to prolate (oval), post drug loading. Cryo-TEM analysis provides a detailed size distribution of both the liposomes (minor and major axes) and the nano-rod drug. Both these values are relevant to the drug performance. In this study, we show that at elevated drug concentration (2.75 mg/ml) the drug grows mainly along the major axis and that this high concentration can result, in some cases, in liposome rupture. We show that the combination of cryo-TEM and DLS constitutes a reliable tool for demonstrating the stability of the formulation in human plasma at body temperature, a characteristic that is crucial for achieving therapeutic efficacy.Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research