Drug-like properties of tyrosine kinase inhibitors in ophthalmology: Formulation and topical availability

Phatsawee Jansook*, Þorsteinn Loftsson, Einar Stefánsson

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Tyrosine kinase inhibitors (TKIs) can inhibit edema and neovascularization, such as in age-related macular degeneration and diabetic retinopathy. However, their topical administration in ophthalmology is limited by their toxicity and poor aqueous solubility. There are multiple types of TKIs, and each TKI has an affinity to more than one type of receptor. Studies have shown that ocular toxicity can be addressed by selecting TKIs that have a high affinity for specific vascular endothelial growth factor receptors (VEGFRs) but a low affinity for epidermal growth factor receptors (EGFRs). Drugs permeate from the aqueous tear fluid into the eye via passive diffusion. Thus, a sustained high concentration of the dissolved drug in the aqueous tear fluid is essential for a successful delivery to posterior tissues such as the retina. Unfortunately, the aqueous solubility of the TKIs that have the most favorable VEGFR/EGFR affinity ratio, that is, axitinib and cabozantinib, is well below 1 µg/mL, making their topical delivery very challenging. This is a review of the drug-like properties of TKIs that are currently being evaluated or have been evaluated as ophthalmic drugs. These properties include their solubilization, cyclodextrin complexation, and ability to permeate from the aqueous tear fluid to the posterior eye segment.

Original languageEnglish
Article number124018
Pages (from-to)124018
Number of pages11
JournalInternational Journal of Pharmaceutics
Publication statusPublished - 25 Apr 2024

Bibliographical note

Copyright © 2024 Elsevier B.V. All rights reserved.

Other keywords

  • Efficacy
  • Eye drops
  • Permeation
  • Solubility
  • Toxicity
  • Tyrosine kinase inhibitor
  • Vascular Endothelial Growth Factor A
  • Protein Kinase Inhibitors
  • Tyrosine Kinase Inhibitors
  • Pharmaceutical Preparations
  • Ophthalmology
  • Administration, Topical


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