Evaluation of Clearance Mechanisms with Transscleral Drug Delivery

초록

PURPOSE. The goal of this study was to examine elimination pathways when delivering subconjunctivally administered hydrophilic agents to the retinas of rat eyes. METHODS. The distribution of sodium fluorescein released from an episcleral implant was compared in live and postmortem eyes. Elimination of the subconjunctivally administered hydrophilic agent IgG through blood and lymphatic vessels was investigated by immunohistochemistry. Additionally, lymphatic elimination of subconjunctivally injected sodium fluorescein was quantitatively evaluated. RESULTS. NaFl released from an episcleral implant was successfully delivered to the subretinal space in the postmortem eye but failed to do so in the live eye. Immunohistochemical visualization of the conjunctival tissue demonstrated dense distribution of blood and lymphatic vessels while also confirming the elimination of subconjunctivally administered IgG through these same vessels. The lymphatic elimination rate after injection of 75.6 mu g of a hydrophilic agent, sodium fluorescein, into the subconjunctival space was determined to be 105 ng/min between 30 and 60 minutes. CONCLUSIONS. Conjunctival blood and lymphatic vessel elimination considerably limit transscleral hydrophilic drug delivery to the retina. (Invest Ophthalmol Vis Sci. 2010;51:5205-5212) DOI:10.1167/iovs.10-5337

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