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Bernard F Godley, Edward Kraft, Zhen-Yang Zhao, Ahmed Elkeeb; Bio-engineered model eye for in-vitro drug permeation using photokinetic delivery. Invest. Ophthalmol. Vis. Sci. 2014;55(13):486.
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© ARVO (1962-2015); The Authors (2016-present)
We describe a synthetic model eye which was developed to address access and variability of scleral tissue samples, and to model transscleral concentration gradient conditions and compositions found in the eye.
The model eye unit was fabricated by bonding a glutaraldehyde cross-linked type-I collagen membrane in a spectrophotometer cuvette with 1% hyaluronic acid as the drug recipient medium. Photokinetic delivery, employing pulsed, low energy incoherent light, was studied by directly illuminating a 1mg/ml methotrexate (MTX) solution placed in the drug donor compartment on top of the membrane with 450nm light at 8.2mW from an LED source pulsed at 25 cycles per second, for 1 hour. Non-illuminated control conditions were maintained similarly except for light illumination. Studies were conducted at 37°C. At the endpoint, a modified UV-visual spectrophotometer was employed to rapidly determine the concentration of MTX adjacent to the membrane at 0mm, and at 1mm and 2mm distal to the membrane within the recipient compartment medium of the model eye.
A defined concentration gradient was observed within the non-agitated drug recipient media progressively diminishing with greater distances from the membrane. Transport of MTX(in µg/ml, mean ±s.d.) through the membrane for the non-illuminated control group vs. photokinetic group showed significantly increased permeation at all depths: at 0mm, 24.7± 3.5 vs. 38.0 ± 2.5*; at 1mm, 11.6 ±2.0 vs. 19.7 ± 1.3* ; and at 2mm 4.0 ± 1.0 vs. 8.2 ± 0.9* , respectively(*p<.001). Scanning electron microscopy (SEM) images showed that no structural damage or shunts on the surface of cross-linked gelatin membrane after one-hour light illumination compared to non-illuminated control membranes.
The application of pulsed non-coherent visible light significantly enhances the permeation of MTX through a cross-linked type 1 collagen membrane into hyaluronic acid. Future studies will determine how closely this synthetic system mirrors transscleral permeation.
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