Preformulation Characterization And Formulation Development of Δ9-Tetrahydrocannabinol Prodrugs For Potential Treatment Of Glacuoma

Relationship between smoking marihuana and a drop in intraocular pressure (IOP) was first reported in 1971. Research efforts since then have identified a number of constituents that could be linked to this observation. Delta-9-Tetrahydrocannabinol (THC) was one of the ingredients identified. However, four decades and numerous research efforts since the first observation, it has still not been concluded whether THC is effective in the treatment of glaucoma or not. Current therapy for IOP control in glaucoma, though effective, cannot prevent vision loss completely. Thus, identification of agents that can lower IOP as well as protect the retinal ganglion cells from apoptosis could yield a new class of anti-glaucoma molecules. Protection of retinal ganglion cells against apoptosis could yield a new class of antiglaucoma agents. Numerous investigations have demonstrated that THC also acts as a neuroprotective agent making it a very promising lead compound. However noninvasive delivery of THC to the targeted intraocular tissues is challenging due to its poor physiochemical properties. The aim of the current project was to effectively deliver THC to the intraocular tissues. THC prodrugs were synthesized to improve physicochemical properties. Preformulation characterization and formulation development for the THC prodrugs was undertaken. A high throughput in vitro model to screen the various formulations for transcorneal permeability was also developed. Promising formulations were instilled in vivo in anesthetized rabbit model and tissue concentrations were determined. Earlier formulations reported in the literature, used for determining efficacy were not observed to deliver THC to the targeted intraocular tissues. The formulations developed in this study were able to deliver significantly higher concentrations to the intraocular tissues. Future studies need to investigate if these improved formulations of THC demonstrate pharmacological activity against glaucoma.

Name thesis:degree_name

Ph.D. in Pharmaceutical Sciences

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biomolecular Sciences

Year dc:date.available

2012

Author dc:creator

• Hingorani, Tushar

Contributors dc:contributor

• Soumyajit Majumdar
• John O'Haver
• Seongbong Jo

• Glaucoma
• Neuroprotection
• Ophthalmic
• Retinal Ganglion Cells
• Tetrahydrocannabinol
• Pharmacy and Pharmaceutical Sciences

Repository record dc:identifier

https://egrove.olemiss.edu/etd/1487

OAI identifier oai:identifier

oai:egrove.olemiss.edu:etd-2486