Micelle-solubilized axitinib for ocular administration in anti-neovascularization

Int J Pharm. 2019 Apr 5:560:19-26. doi: 10.1016/j.ijpharm.2019.01.051. Epub 2019 Jan 30.

Abstract

The development of new blood vessels is directly related to the occurrence of eye diseases. Anti-angiogenic drugs can theoretically be extended to the treatment of ophthalmic diseases. In this study, axitinib, a class of tyrosine kinase inhibitors, was loaded via the amphiphilic copolymer MPEG-PCL, improving its dispersibility in water. Axitinib-loaded micelles showed low toxicity in concentration gradient assays. Additionally, multiple doses by scratch assay confirmed that axitinib had no significant effect on normal cell migration, and biosafety test results showed good cell compatibility. After we established the corneal neovascularization model after an alkali burn in rats, the anti-angiogenic efficacy was tested, with dexamethasone as a positive control. The results showed that axitinib-loaded micelles had anti-angiogenic effects without obvious tissue toxicity. As a class of targeted tyrosine kinase inhibitors, axitinib can be used in the treatment of ocular neovascular diseases through nanocrystallization.

Keywords: Anti-angiogenesis; Axitinib; Micelles; Ophthalmic drug delivery.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Ophthalmic
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Axitinib / administration & dosage
  • Axitinib / pharmacology*
  • Cell Movement
  • Dexamethasone / pharmacology
  • Disease Models, Animal
  • Drug Carriers / chemistry
  • Male
  • Micelles
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Polyesters / chemistry
  • Polyethylene Glycols / chemistry
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology*
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Angiogenesis Inhibitors
  • Drug Carriers
  • Micelles
  • Polyesters
  • Protein Kinase Inhibitors
  • methoxy poly(ethylene glycol-co-epsilon-caprolactone)
  • Polyethylene Glycols
  • Dexamethasone
  • Axitinib