Exploration in the Effectiveness of Solid Lipid Nanoparticle Formulations in Enhancing Ocular Delivery of Win 55, 212 in the Management of Glaucoma

Nesbit, Emily Ann (2016) Exploration in the Effectiveness of Solid Lipid Nanoparticle Formulations in Enhancing Ocular Delivery of Win 55, 212 in the Management of Glaucoma. Undergraduate thesis, under the direction of Soumyajit Majumdar from Pharmaceutics and Drug Delivery, The University of Mississippi.

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Abstract

Glaucoma is a progressive and degenerative ocular disease which, without proper treatment, can result in permanent blindness. Due to a complex organization of lipophilic and hydrophilic ocular membranes, topical delivery of therapeutic agents has also proved to be a challenging task. Cannabinoids, such as Δ9-Tetrahydrocannabinol (THC), have intraocular pressure (IOP) lowering and neuroprotective capabilities. Due to the unfavorable physiochemical characteristics of these molecules, delivery into the eye through a topical route is very difficult. Previous research has shown that prodrug derivatization and formulations such as solid lipid nanoparticles (SLNs) improve the physiochemical characteristics and ocular bioavailability of such molecules. WIN 55, 212 (WIN) is a synthetic cannabinoid possessing a structure similar to THC and is fifty times more potent. WIN 55, 212 (212) also possesses slightly better physiochemical characteristics than THC. The goal of this research is to develop solid lipid nanoparticle formulations that will enhance the intraocular delivery of WIN 55, 212. The particle size, entrapment efficiency, and content of the SLN formulations will be standardized. In vitro and in vivo studies will be carried out to determine the benefit of the SLNs over conventional formulations. In vitro transcorneal permeability studies will be carried out utilizing a Franz diffusion apparatus and corneas dissected from rabbit eyes. Samples will be taken at different time intervals throughout the permeability study and analyzed using a HPLC-UV system. The in vivo IOP lowering evaluation studies will be performed on male New Zealand albino rabbits that have artificially induced glaucoma. Fifty microliters of 0.4% w/v SLN’s (Dose: 0.2 mg) will be topically applied to the cul-de-sac of each rabbit’s eye. An equivalent dose of WIN 55, 212 in Tocrisolve® will be used as the control. The study will take place until the IOP returns to 90% of the baseline levels. Following the conclusion of the study, the animals will be anesthetized and euthanized with a sufficient dose of pentobarbital injected through the marginal ear vein. Immediately, the eyes will be enucleated and the ocular tissues will be isolated, weighed, and analyzed for WIN 55, 212 content. The goal of this project is to increase the retention of WIN 55, 212 in the eye and prolong the intraocular lowering duration compared to the control formulation.

Item Type: Thesis (Undergraduate)
Creators: Nesbit, Emily Ann
Student's Degree Program(s): B.S. Pharmaceutical Sciences
Thesis Advisor: Soumyajit Majumdar
Thesis Advisor's Department: Pharmaceutics and Drug Delivery
Institution: The University of Mississippi
Subjects: R Medicine > RE Ophthalmology
R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Depositing User: Emily A Nesbit
Date Deposited: 25 May 2016 16:03
Last Modified: 25 May 2016 16:03
URI: http://thesis.honors.olemiss.edu/id/eprint/648

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