Quantitative Cryo-TEM Reveals New Structural Details of Doxil-Like PEGylated Liposomal Doxorubicin Formulation.

Nano-drugs based on nanoparticles (NP) or on nano-assemblies as carriers of the active pharmaceutical ingredient (API) are often expected to perform better compared to conventional dosage forms. Maximum realization of this potential though requires optimization of multiple physico-chemical, including structural and morphological, parameters. Meaningful distributions of these parameters derived from sufficient populations of individual NPs rather than ensemble distributions are desirable for this task, provided that relevant high-resolution data is available.

Cardinal Role of Intraliposome Doxorubicin-Sulfate Nanorod Crystal in Doxil Properties and Performance.

The uniqueness of Doxil can be attributed, to a large extent, to its intraliposomal doxorubicin-sulfate nanorod crystal. We re-examine these nanocrystal features and their mechanism of the formation by studying pegylated liposomal doxorubicins (PLDs) of the same lipid composition, size distribution, and extraliposome medium that were prepared at different ammonium sulfate (AS) concentrations. This study includes a comparison of the thermotropic behavior, morphology, and in vitro ammonia-induced doxorubicin release (relevant to Doxil's in vivo performance) of these PLDs.

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

Size and morphology distributions are critical to the performance of nano-drug systems, as they determine drug pharmacokinetics and biodistribution. Therefore, comprehensive and reliable analyses of these properties are required by both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). 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.