Physical characterization of liposomal drug formulations using multidetector asymmetrical-flow field flow fractionation
Jeremie Parot, Fanny Caputo, Dora Mehn, Vincent A. Hackley, Luigi Calzolai
Liposomal formulations for the treatment of cancer and other diseases are the most common form of nanotechnology enabled pharmaceuticals (NEPs) submitted for market approval and in clinical application today. The accurate characterization of their physical-chemical properties is a key requirement, in particular size, size distribution, shape, and physical-chemical stability are properties that regulators identify as critical quality attributes. Here we report a standardized method, based on multi-detector asymmetrical-flow field flow fractionation (MD- AF4) to accurately and reproducibly separate liposomal drug formulations into their component populations and to characterize their associated size and size distribution, whether monomodal or polymodal in nature. In addition, the results show that the method is suitable to measure liposomes in the presence of serum proteins and can yield information on the shape and physical stability of the structures. The optimized MD-AF4 based method has been validated across different instrument platforms, laboratories, and drug formulations following a comprehensive analysis of factors that influence the fractionation process and physical characterization. Interlaboratory reproducibility and intra-laboratory precision were evaluated, identifying sources of bias and establishing criteria for the acceptance of results. This method meets a documented high priority need in regulatory science as applied to NEPs such as Doxil and can be adapted to the measurement of other NEP forms (such as lipid nanoparticle therapeutics) with some modifications. Overall, this standardized method will help researchers to obtain a more complete understanding of key physical properties of NEPs, and regulatory agencies will benefit from the structured and validated approach, ultimately leading to faster translation of innovative research to clinical trials.
, Caputo, F.
, Mehn, D.
, Hackley, V.
and Calzolai, L.
Physical characterization of liposomal drug formulations using multidetector asymmetrical-flow field flow fractionation, Journal of Controlled Release, [online], https://doi.org/10.1016/j.jconrel.2020.01.049, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=929175
(Accessed October 3, 2022)