ArticleInvestigative ophthalmology & visual science2017
Development of a Δ9-Tetrahydrocannabinol Amino Acid-Dicarboxylate Prodrug With Improved Ocular Bioavailability.
Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 54 citations in OpenAlex.
- Review
- Cannabinoids as Multitarget Drugs for the Treatment of Autoimmunity in Glaucoma.ACS pharmacology & translational science · 2025Review
- Adverse Ocular Impact and Emerging Therapeutic Potential of Cannabis and Cannabinoids: A Narrative Review.Clinical ophthalmology (Auckland, N.Z.) · 2024Review
- Bilateral Optic Neuropathy Associated with Acute Inhaled Marijuana Use: Case Report and Review of the Literature.Neuro-ophthalmology (Aeolus Press) · 2024Article
- The Skin and Natural Cannabinoids-Topical and Transdermal Applications.Pharmaceuticals (Basel, Switzerland) · 2023Review
- LC-MS/MS quantitation of non-psychotropic cannabinoid cannabidiol in aqueous humor.Journal of pharmaceutical and biomedical analysis · 2023Article
- Cannabinoid-Based Ocular Therapies and Formulations.Pharmaceutics · 2023Review
- Cannabidiol Loaded Topical Ophthalmic Nanoemulsion Lowers Intraocular Pressure in Normotensive Dutch-Belted Rabbits.Pharmaceutics · 2022Article
- Development and evaluation of polycaprolactone-based electrospun nanofibers containing timolol maleate as a sustained-release device for treatment of glaucoma:Research in pharmaceutical sciences · 2022Article
- The Transdermal Delivery of Therapeutic Cannabinoids.Pharmaceutics · 2022Review
- Topical Drug Delivery to the Posterior Segment of the Eye.Pharmaceutics · 2022Review
- Elevated IOP Alters the Material Properties of Sclera and Lamina Cribrosa in Monkeys.Disease markers · 2022Article
- Cannabidiol-Loaded Mixed Polymeric Micelles of Chitosan/Poly(Vinyl Alcohol) and Poly(Methyl Methacrylate) for Trans-Corneal Delivery.Pharmaceutics · 2021Article
- Effect of surfactant concentration and sterilization process on intraocular pressure-lowering activity of ΔDrug delivery and translational research · 2021Article
- Review
- The Relationship Between Plasma Tetrahydrocannabinol Levels and Intraocular Pressure in Healthy Adult Subjects.Frontiers in medicine · 2021Article
- Ten Years of Knowledge of Nano-Carrier Based Drug Delivery Systems in Ophthalmology: Current Evidence, Challenges, and Future Prospective.International journal of nanomedicine · 2021Review
- ΔTranslational vision science & technology · 2019Article
- High drug payload nanoparticles formed from dexamethasone-peptide conjugates for the treatment of endotoxin-induced uveitis in rabbit.International journal of nanomedicine · 2019Article
- Curcumin-loaded Nanostructured Lipid Carriers for Ocular Drug Delivery: Design Optimization and Characterization.Journal of drug delivery science and technology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Purpose: The aim of the present study was to evaluate the utility of the relatively hydrophilic Δ9-tetrahydrocannabinol (THC) prodrugs, mono and di-valine esters (THC-Val and THC-Val-Val) and the amino acid (valine)-dicarboxylic acid (hemisuccinate) ester (THC-Val-HS), with respect to ocular penetration and intraocular pressure (IOP) lowering activity. THC, timolol, and pilocarpine eye drops were used as controls. Methods: THC-Val, THC-Val-Val, and THC-Val-HS were synthesized and chemically characterized. Aqueous solubility and in vitro transcorneal permeability of THC and the prodrugs, in the presence of various surfactants and cyclodextrins, were determined. Two formulations were evaluated for therapeutic activity in the α-chymotrypsin induced rabbit glaucoma model, and the results were compared against controls comprising of THC emulsion and marketed timolol maleate and pilocarpine eye drops. Results: THC-Val-HS demonstrated markedly improved solubility (96-fold) and in vitro permeability compared to THC. Selected formulations containing THC-Val-HS effectively delivered THC to the anterior segment ocular tissues in the anesthetized rabbits: 62.1 ng/100 μL of aqueous humor (AH) and 51.4 ng/50 mg of iris ciliary bodies (IC) (total THC). The duration and extent of IOP lowering induced by THC-Val-HS was 1 hour longer and 10% greater, respectively, than that obtained with THC and was comparable with the pilocarpine eye drops. Timolol ophthalmic drops, however, exhibited a longer duration of activity. Both THC and THC-Val-HS were detected in the ocular tissues following multiple dosing of THC-Val-HS in conscious animals. The concentration of THC in the iris-ciliary bodies at the 60- and 120-minute time points (53 and 57.4 ng/50 mg) were significantly greater than that of THC-Val-HS (24.2 and 11.3 ng/50 mg). Moreover, at the two time points studied, the concentration of THC was observed to increase or stay relatively constant, whereas THC-Val-HS concentration decreased by at least 50%. A similar trend was observed in the retina-choroid tissues. Conclusions: A combination of prodrug derivatization and formulation development approaches significantly improved the penetration of THC into the anterior segment of the eye following topical application. Enhanced ocular penetration resulted in significantly improved IOP-lowering activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.