The Global Characterisation of a Drug-Dendrimer Conjugate - PEGylated poly-lysine Dendrimer

The recent emergence of drug-dendrimer conjugates within pharmaceutical industry research and development introduces a range of challenges for analytical and measurement science. These molecules are very high molecular weight (100-200kDa) with a significant degree of structural complexity. The characteristics and quality attributes that require understanding and definition, and impact efficacy and safety, are diverse. They relate to the intact conjugate, the various building blocks of these complex systems and the level of the free and bound active pharmaceutical ingredient (API). From an analytical and measurement science perspective, this necessitates the measurement of the molecular weight, impurity characterisation, the quantitation of the number of conjugated versus free API molecules, the determination of the impurity profiles of the building blocks, primary structure and both particle size and morphology. Here we report the first example of a global characterisation of a drug-dendrimer conjugate - PEGylated polylysine dendrimer currently under development (AZD0466). The impact of the wide variety of analytical and measurement techniques on the overall understanding of this complex molecular entity is discussed, with the relative capabilities of the various approaches compared. The results of this study are an essential platform for the research and development of the future generations of related dendrimer-based medicines. (c) 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.

Automated summary

The recent emergence of drug-dendrimer conjugates presents analytical and measurement challenges in the pharmaceutical industry. These complex molecules have high molecular weights and diverse characteristics. The understanding and definition of their characteristics and quality attributes, which impact efficacy and safety, require measurement of molecular weight, impurity characterization, quantification of conjugated versus free API molecules, determination of impurity profiles, primary structure, particle size, and morphology. This study provides a global characterization of a drug-dendrimer conjugate and discusses the impact of various analytical and measurement techniques on understanding this complex molecular entity. The results are crucial for the future development of dendrimer-based medicines.