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Karen E. Schmitt, Eva Harth, Julie Dobish, Martha-Conley Ingram, Rebecca Sappington, Louise Mawn, Robert Galloway; Design of an In Vitro System to Assess the Potential of a Novel Nanoparticle Drug Delivery System to Cross the Optic Nerve Meninges. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4674.
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Optic neuropathies are a leading cause of irreversible blindness. An obstacle to clinical application of promising drug therapies for optic neuropathies is a viable route of delivery to the site of pathologic change, ganglion cell axons. A solution could be application directly to the optic nerve with (1) penetration of the meninges and (2) extended duration of therapeutic effect. A novel nanosponge has been created by Dr. Eva Harth that can transport drug cargo to selected targets with controlled rate of drug release. The goal of this project is to design a system to test the potential of the nanosponge to cross the optic nerve meninges.
A Perma-Gear Side-Bi-Side cell was selected as the foundation of a dual-chambered temperature-controlled diffusion system to allow introduction of various partitions: a semipermeable membrane in initial experiments, then mammalian, and, ultimately, human optic nerve meninges. A 50 nm functionalized polyester nanoparticle was synthesized and Alexa 546 dye attached. The blood-CSF barrier maintained by the arachnoid barrier cell layer contains pores of several micrometers at the distal optic nerve sheath. Therefore, a Nucleopore membrane with lesser porosity of 0.2 µm was obtained to be used to test the control. Artificial CSF was prepared and supersaturated with 95% O2/5% CO2. Physiologic conditions are reproduced where possible in order to promote integrity of meningeal tissue when it is eventually incorporated as the barrier.
Using UV-Vis Spectroscopy nanodrop method, a concentration curve of particles bound to Alexa Fluor 546 was determined by infrared absorbance to facilitate measurement of diffused nanosponge. The dual-chambered diffusion system was constructed with the Nucleopore membrane in place. We found that after 18 hours 40% of the particles had diffused with completion of diffusion in 24 hours.
We have successfully designed a system that will allow for the testing of a variety of nanoparticles for in vitro optimization of drug delivery to the optic nerve axons through the optic nerve meninges for the ultimate goal of delivering neuroprotective drugs.
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