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

Abstract

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.
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Category

Academic article

Language

English

Author(s)

  • Silvia Sonzini
  • Fanny Caputo
  • Dora Mehn
  • Luigi Calzolai
  • Sven Even Borgos
  • Astrid Hyldbakk
  • Kevin Treacher
  • Weimin Li
  • Mark Jackman
  • Najet Mahmoudi
  • M. Jayne Lawrence
  • Claire Patterson
  • David Owen
  • Marianne B Ashford
  • Nadim Akhtar

Affiliation

  • SINTEF Industry / Biotechnology and Nanomedicine
  • Université Grenoble Alpes
  • European Commission - Joint Research Centre
  • University of Manchester
  • AstraZeneca UK
  • CCLRC Rutherford Appleton Laboratory
  • Australia

Year

2023

Published in

International Journal of Pharmaceutics

ISSN

0378-5173

Volume

637

View this publication at Norwegian Research Information Repository