| Endophthalmitis, inflammation of internal ocular tissues, is often linked to poor surgical technique, contaminated intraocular lenses or penetrating ocular injuries. It is characterized by a decrease in visual acuity, severe pain and, if not treated, may lead to loss of vision. The risks associated with ocular tissue damage present a challenge in selecting a suitable drug delivery vehicle that can deliver the optimal therapeutic dose while minimizing further loss of tissue-function efficiency.;Voriconazole, a tri-azole drug administered currently via oral and intravenous infusion, has been shown to be a good alternative for treatment of fungal infections due to its broad spectrum of activity against a variety of fungi such as Candida spp., Aspergillus spp., Cryptococcus neoformans, Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, Fusarium spp. and Pennicillium marneffei. Most commonly used for antifungal treatment is Amphotericin B, which is often associated with organ toxicity at therapeutic levels e.g. irreversible kidney toxicity, increased liver enzymes, hepatotoxicity, cardiac arrest, skin reaction and electrolyte imbalance. AmBisome, a liposomal formulation of Amphotericin B mitigates some of these side effects while intrinsically possessing comparable anti-fungal efficacy. The drawbacks of use, however, are its expense and liposome-associated instability.;Voriconazole, at the doses used in the current modes of treatment, is associated with several side effects including transient visual disturbances, sepsis, diarrhea, peripheral edema, respiratory disorder and elevated hepatic enzyme levels. By reducing the dose administered, the risks and side effects associated with Voriconazole can be reduced.;Pluronic F127 and Tetronic 1107 are block copolymers of polyethylene oxide and polypropylene oxide and structurally have terminating primary hydroxyl groups. These chemical entities are also biodegradable and exhibit low toxicity. The amphiphilic nature of these polymers is attributed to the lipophilic PPO blocks covalently linked to the more hydrophilic PEO subunits. At concentrations between 15%--30%, solutions of F127 and Tetronic 1107 exhibit thermogelation i.e. as the temperature is increased, these micellar aqueous solutions gradually transition into gel-like matrices.;It was proposed that thermogeling systems can be used to deliver efficacious concentrations of Voriconazole to the ocular region by targeting drug administration to the site of action. The specific aims and milestones described in this manuscript support a feasible platform for delivery of Voriconazole to the vitreous humor at therapeutic levels capable of treating post-surgical invasive endophthalmitis, while also reducing the side effects associated with current modes of treatment. The proposed delivery vehicle will also minimize systemic tissue exposure associated with the current oral and/or intravenous modes of Voriconazole administration. |
