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E. M. Harth, A. E. van der Ende, L. A. Mawn; Trojan Horse Nanoparticle Delivery Vehicles. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3489.
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To address the rapid evolution of resistance of corneal microbials to the Quinolones, we have investigated the possibility of using a novel nanosponge designed for targeted drug delivery for radiation guided therapy. This novel nanosponge1,2 can deliver drugs trapped within the structure of the sponge.
In our preliminary studies, we determined the efficiency of the modular nanoparticle system using a dye labeled molecular transporter in an in vitro model. Five adult Sprague-Dawley rats were sacrificed by lethal inhalation of CO2. At the moment of euthanasia, eight eyes of four rats were treated with a solution of 2x10-2 M nanoparticle, one rat served as the no treatment control. The eye globes with attached optic nerves were fixed and then were cut into 4-µm sections and were stained with traditional DAPI dye. Slides were viewed at 40× magnification using a digital fluorescent microscope and imaged to visualize Alexa Fluor 594-labeled transporter. Background autofluorescence was subtracted and the settings were held constant for both the control and the treatment eyes.
The cornea of the no treatment eyes did not show any fluorescence corresponding to the Alexa Fluor dye, whereas the treated eyes showed consistent corneal adherence visualized through the Alexa 594 dye.
We can conclude that the surface like modification, which is similar to a viral envelope, can work like a Trojan horse to attach and then penetrate the infected tissue and release high quantities of the drug. This feature will be a powerful attribute to develop efficient treatments of infectious keratitis. Similar to viruses, the surface of the nanosponge has surface attachments which allows for enhanced tissue penetration.1,2 These two features, one which allows for increased drug concentration in the tissue and the other which allows for increased tissue penetration are critical to successfully over come drug resistance. Future studies will include incorporating a quinolone into the nanosponge and determining the efficiency and amount of quinolone that can be transported into the cornea.
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