title: Ocular Disposition of ∆8-Tetrahydrocannabinol from Various Topical Ophthalmic Formulations.
abstract: The purposes of this project are to enhance the trans-membrane penetration of Δ8-Tetrahydrocannabinol (Δ8-THC) and to study the effect of various lipid based systems in delivering the compound, non-invasively, to anterior and posterior ocular chambers. Solid lipid nanoparticles (SLNs), fast gelling films were manufactured using high pressure homogenization and melt cast techniques, respectively. The formulations were characterized for drug content, entrapment efficiency, particle size and subsequently evaluated in vitro for trans-corneal permeation. In vivo, the drug disposition was tested via topical administration in albino rabbits. The eye globes were enucleated at the end of experiment and tissues were analyzed for drug content. All formulations showed favorable physicochemical characteristics in terms of particle size, entrapment efficiency, and drug content. In vitro, the formulations exhibited a transcorneal flux that depended on the formulation's drug load. An increase in drug load from 0.1 to 0.75% resulted in 12- to16-folds increase in permeation. In vivo, the film was able to deliver THC to all the tissues with high accumulations in cornea and sclera. The SLNs showed a greater ability in delivering THC to all the tissues, at a significantly lower drug load, due to their colloidal size range, which in turn enhanced corneal epithelial membrane penetration. The topical formulations evaluated in the present study were able to successfully deliver Δ8-THC in therapeutically meaningful concentrations (EC50values for CB1: 6 nM and CB2: 0.4 nM) to all ocular tissues except the vitreous humor, with pronounced tissue penetration achieved using SLNs as a Δ8-THC delivery vehicle.
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, 111 Faser Hall, University, Mississippi, 38677, USA.
authors.forename: Nagendra S
authors.initials: NS
authors.lastname: Punyamurthula
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, 111 Faser Hall, University, Mississippi, 38677, USA.
authors.forename: Goutham R
authors.initials: GR
authors.lastname: Adelli
authors.affiliation: ElSohly Laboratories Inc., 5-Industrial Park Drive, Oxford, Mississippi, 38655, USA.
authors.forename: Waseem
authors.initials: W
authors.lastname: Gul
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, 111 Faser Hall, University, Mississippi, 38677, USA.|Research Institute of Pharmaceutical Sciences, University of Mississippi, 111 Faser Hall, University, Mississippi, 38677, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, 111 Faser Hall, University, Mississippi, 38677, USA.|ElSohly Laboratories Inc., 5-Industrial Park Drive, Oxford, Mississippi, 38655, USA.|Research Institute of Pharmaceutical Sciences, University of Mississippi, 111 Faser Hall, University, Mississippi, 38677, USA.
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: ElSohly
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, 111 Faser Hall, University, Mississippi, 38677, USA. majumso@olemiss.edu.|Research Institute of Pharmaceutical Sciences, University of Mississippi, 111 Faser Hall, University, Mississippi, 38677, USA. majumso@olemiss.edu.
authors.forename: Soumyajit
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D060433:Administration, Ophthalmic; D000287:Administration, Topical; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism*; D013759:Dronabinol / Q000008:administration & dosage* / Q000378:metabolism*; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011817:Rabbits
chemical_list: D018712:Analgesics, Non-Narcotic; D013759:Dronabinol
keywords: lipid-based drug delivery; ocular drug delivery; ocular films; solid lipid nanoparticles; tetrahydrocannabinol