In depth characterization of physicochemical critical quality attributes of a clinical drug-dendrimer conjugate

[Display omitted] •Drug-dendrimer conjugates are complex drug delivery systems which fall under the nanomaterials family.•The physicochemical characterization of AZD0466, a drug-dendrimer conjugate in clinical trials, by orthogonal techniques is reported.•The results helped to identify the stage and techniques to use to measure Critical Quality Attributes (CQAs) of drug-dendrimer conjugates. A deep and detailed understanding of drug-dendrimer conjugates key properties is needed to define the critical quality attributes that affect drug product performance. The characterization must be executed both in the formulation media and in biological matrices. This, nevertheless, is challenging on account of a very limited number of suitable, established methods for characterizing the physicochemical properties, stability, and interaction with biological environment of complex drug-dendrimer conjugates. In order to fully characterize AZD0466, a drug-dendrimer conjugate currently under clinical development by AstraZeneca, a collaboration was initiated with the European Nanomedicine Characterisation Laboratory to deploy a state-of-the-art multi-step approach to measure physicochemical properties. An incremental complexity characterization approach was applied to two batches of AZD0466 and the corresponding dendrimer not carrying any drug, SPL-8984. Thus, the aim of this work is to guide in depth characterization efforts in the analysis of drug-dendrimer conjugates. Additionally, it serves to highlight the importance of using the adequate complementary techniques to measure physical and chemical stability in both simple and biological media, to drive a complex drug-dendrimer conjugate product from discovery to clinical development.