Dissecting the stability of Atezolizumab with renewable amino acid-based ionic liquids: Colloidal stability and anticancer activity under thermal stress

Bayan Alkhawaja, Faisal Al-Akayleh, Zaid Al-Rubaye, Ghayda' AlDabet, Muna Bustami, Maisa’a Smairat, Ahmed S.A.A. Agha, Jehad Nasereddin, Nidal Qinna, Andreas Michael, Andrew Watts

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Abstract

Monoclonal antibodies (mAbs) have revolutionised the biopharmaceutical market. Being proteinaceous, mAbs are prone to chemical and physical instabilities. Various approaches were attempted to stabilise proteins against degradation factors. Ionic liquids (ILs) and deep eutectic solvents (DESs) have been established as green solvents for ever-increasing pharmaceutical and biopharmaceutical applications. Hence, amino acid (AA)-based ILs, were used for the first time, for mAb stabilisation. Choline (Ch)-based DESs were also utilised for comparison purposes. The prepared ILs and DESs were utilised to stabilise Atezolizumab (Amab, anti-PDL-1 mAb). The formulations of Amab in ILs and DESs were incubated at room temperature, 45 or 55 °C. Following this, the structural stability of Amab was appraised. Interestingly, Ch-Valine retained favourable structural stability of Amab with minimal detected aggregation or degradation as confirmed by UV–visible spectroscopy and protein Mass Spectroscopy. The measured hydrodynamic diameter of Amab in Ch-Valine ranged from 10.40 to 11.65 nm. More interestingly, the anticancer activity of Amab was evaluated, and Ch-Valine was found to be optimum in retaining the activity of Amab when compared to other formulations, including the control Amab sample. Collectively, this study has spotlighted the advantages of adopting the Ch-AA ILs for the structural and functional stabilising of mAbs.
Original languageEnglish
Article number132208
JournalInternational Journal of Biological Macromolecules
Volume270
Early online date8 May 2024
DOIs
Publication statusE-pub ahead of print - 8 May 2024

Keywords

  • Amino acid-based ILs
  • Atezolizumab
  • Biocompatible and renewable ILs
  • Deep eutectic solvents
  • Ionic liquids
  • Stability of monoclonal antibodies

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology
  • Biochemistry

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