Ocular biodistribution of cysteamine delivered by a sustained release microsphere/thermoresponsive gel eyedrop

Int J Pharm. 2022 Aug 25:624:121992. doi: 10.1016/j.ijpharm.2022.121992. Epub 2022 Jul 7.

Abstract

The objective of the investigation was to determine the ocular biodistribution of cysteamine, a reducing agent used for treatment of cystine crystals in cystinosis, following topical administration of a sustained release formulation and traditional eyedrop formulation. To the right eye only, rabbits received a 50 µL drop of 0.44% cysteamine eyedrops at one drop per waking hour for 2, 6, 12, and 24 h. A second group received one 100 µL drop of a sustained release formulation containing encapsulated cysteamine microspheres suspended in a thermoresponsive gel. Upon serial sacrifice, ocular tissues from both eyes and plasma were obtained and quantified for cysteamine using LC-MS/MS. Cysteamine was detected in the cornea, aqueous humor and vitreous humor. Systemic plasma concentrations of cysteamine from treatment groups were below the limit of detection. As expected, 0.44% cysteamine eyedrops when administered hourly maintained drug concentrations within the cornea at a magnitude 5 times higher than a single dose of the sustained release formulation over 12 h. The sustained release formulation maintained cysteamine presentation across 12 h from a single drop. These studies demonstrate distribution of cysteamine to the eye following topical administration, including high drug uptake to the cornea and low systemic distribution.

Keywords: Cornea; Ocular drug delivery; Ophthalmic formulations; Rare disease; Translational research.

MeSH terms

  • Animals
  • Chromatography, Liquid
  • Cornea
  • Cysteamine* / chemistry
  • Cystinosis* / drug therapy
  • Delayed-Action Preparations / therapeutic use
  • Microspheres
  • Ophthalmic Solutions
  • Rabbits
  • Tandem Mass Spectrometry
  • Tissue Distribution

Substances

  • Delayed-Action Preparations
  • Ophthalmic Solutions
  • Cysteamine