Stability of cell-penetrating peptide anti-VEGF formulations for the treatment of age-related macular degeneration

Naa Dei Nikoi, Matthew Berwick, Jack A. Bryant, Lily Riordan, Louise Slope, Anna F.A. Peacock, Felicity de Cogan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Aim: The development of a polyarginine cell-penetrating peptide (CPP) could enable the treatment of age-related macular degeneration, with drugs like bevacizumab, to be administered using eye drops instead of intravitreal injections. Topical formulations have a vast potential impact on healthcare by increasing patient compliance while reducing the financial burden. However, as the ocular preparations may contain several doses, it is essential to understand the stability of the bevacizumab+CPP conjugate produced. 

Materials and Methods: In this work, we examine the stability of a bevacizumab solution with and without cell-penetrating peptide using dynamic light scattering and circular dichroism to assess the physical stability. We use HPLC to assess the chemical stability and ELISA to assess its biological activity. We also examine the potential of the CPP to be used as an antimicrobial agent in place of preservatives in the eye drop. 

Results: The structural stability of bevacizumab with and without the CPP was found not to be affected by temperature: samples stored at either 20°C or 4°C were identical in behavior. However, physical instability was observed after five weeks, leading to aggregation and precipitation. Further investigation revealed that the addition of the polypeptide led to increased aggregation, as revealed through dynamic light scattering and concentration analysis of the peptide through HPLC. Complexing the bevacizumab with CPP had no effect on biological stability or degradation.

Conclusions: Our findings suggest that the shelf life of CPP+bevacizumab complexes is at least 38 days from its initial formulation. Currently, the mechanism for aggregation is not fully understood but does not appear to occur through chemical degradation.

Original languageEnglish
Pages (from-to)751-757
JournalCurrent eye research
Issue number5
Early online date25 Apr 2021
Publication statusPublished - May 2021

Bibliographical note

Funding Information:
This work has been funded by a Wellcome Trust Pathfinder Award, the University of Birmingham and the Pharmacy Department, University Hospitals Coventry and Warwickshire NHS Trust.


  • cell-penetrating peptide (CPP)
  • eye drops
  • Ocular drug delivery
  • stability
  • vascular endothelial growth factor (VEGF)

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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