The dose-dependent effect of a stabilized cannabidiol nanoemulsion on ocular surface inflammation and intraocular pressure

Leslie Rebibo, Marina Frušić-Zlotkin, Ron Ofri, Taher Nassar, Simon Benita*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Cannabidiol (CBD) is a phytocannabinoid that has a great clinical therapeutic potential. Few studies have been published on its efficacy in ocular inflammations while its impact on intraocular pressure (IOP), a major risk factor for glaucoma, remains unclear. Moreover, due to its lability and high lipophilicity, its formulation within a prolonged stable topical ophthalmic solution or emulsion able to penetrate the highly selective corneal barrier is challenging. Therefore, various CBD nanoemulsions (NEs) were designed and evaluated for stability in accelerated conditions. Further, the optimal formulation was tested on a murine LPS-induced keratitis inflammation model. Lastly, increasing CBD concentrations were topically applied, for two weeks, on mice eyes, for IOP measurement. CBD NEs exhibited optimal physicochemical characteristics for ocular delivery. A specific antioxidant was required to obtain the stable, final, formulation. In vivo, 0.4 to 1.6% CBD w/v reduced the levels of key inflammatory cytokines, depending on the concentration applied. These concentrations decreased or did not affect the IOP. Our results showed that a well-designed CBD ocular dosage form can be stabilized for an extended shelf life. Furthermore, the significant decrease in inflammatory cytokines levels could be exploited, provided that an adequate therapeutic dosage regimen is identified in humans.

Original languageAmerican English
Article number121627
JournalInternational Journal of Pharmaceutics
Volume617
DOIs
StatePublished - 5 Apr 2022

Bibliographical note

Funding Information:
We would like to thank Dr. Yoram Soroka for his technical assistance. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Publisher Copyright:
© 2022 Elsevier B.V.

Copyright © 2022 Elsevier B.V. All rights reserved.

Keywords

  • Cannabidiol
  • Inflammation
  • Intraocular pressure
  • Nanoemulsion
  • Ocular
  • Animals
  • Glaucoma/drug therapy
  • Inflammation/chemically induced
  • Intraocular Pressure
  • Mice
  • Ophthalmic Solutions/pharmacology

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