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

• DOI: 10.1167/tvst.8.5.15
• Publication Date: 2019-09-19T14:30:32Z
• Authors: Pranjal S. Taskar; Akash Patil; Prit Lakhani; Eman Ashour; Waseem Gul; Mahmoud A. ElSohly; Brian Murphy; Soumyajit Majumdar
• Keywords: Pilocarpine; Eye drop; Solid lipid nanoparticle

Purpose: Δ9-Tetrahydrocannabinol-valine-hemisuccinate, a hydrophilic prodrug of Δ9-tetrahydrocannabinol, synthesized with the aim improving ocular bioavailability parent molecule, was investigated in lipid-based nanoparticle dosage form for delivery. Methods: Solid lipid nanoparticles (SLNs) Δ9-tetrahydrocannabinol-valine-hemisuccinate and along nanoemulsion Δ9-tetrahydrocannabinol-valine-hemisuccinate, were tested glaucoma management normotensive rabbit model by using multiple-dosing protocol. Marketed formulations timolol maleate pilocarpine HCl also their pharmacodynamic profile, post-single dose administration. Results: A peak intraocular pressure (IOP) drop 30% from baseline observed rabbits treated SLNs loaded at 90 minutes. Treated eyes receiving had significantly lower IOP than untreated until 360 minutes, whereas group emulsion formulation showed minutes only. In comparison to marketed ophthalmic solutions, produced greater effect on terms both intensity duration. tissue concentrations, higher concentrations iris-ciliary bodies retina-choroid SLNs. Conclusion: Δ9-Tetrahydrocannabinol-valine-hemisuccinate formulated nanoparticulate carrier shows promise pharmacotherapy. Translational Relevance: Glaucoma therapies usually focus decreased aqueous humor production increased outflow. However, such therapy is not curative, there lies need preclinical research efforts agents that only affect dynamics but provide neuroprotection. Historically, have been bench-scale studies looking retinal ganglion cell death post-axonal injury. smooth translation this vitro activity clinic, animal models examining reduction, i.e., connecting neuroprotective measurable outcome (IOP), be investigated. This study reduction efficacy cannabinoids pharmacotherapy model, bringing forth new class potential improved permeation back eye, possibly providing benefits management.