Δ9-Tetrahydrocannabinol Derivative-Loaded Nanoformulation Lowers Intraocular Pressure in Normotensive Rabbits

Abstract Purpose: Δ9-Tetrahydrocannabinol-valine-hemisuccinate, a hydrophilic prodrug of Δ9-tetrahydrocannabinol, synthesized with the aim of improving the ocular bioavailability of the parent molecule, was investigated in a lipid-based nanoparticle dosage form for ocular delivery. Methods: Solid lipid nanoparticles (SLNs) of Δ9-tetrahydrocannabinol-valine-hemisuccinate and Δ9-tetrahydrocannabinol, along with a nanoemulsion of Δ9-tetrahydrocannabinol-valine-hemisuccinate, were tested for glaucoma management in a normotensive rabbit model by using a multiple-dosing protocol. Marketed formulations of timolol maleate and pilocarpine HCl were also tested for their pharmacodynamic profile, post-single dose administration.