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R. M. Burr, S. A. Molokhia, C. J. Bishop, H. J. Sant, J. M. Simonis, B. K. Gale, B. K. Ambati; In vitro Diffusion and Permeability of a Novel Intraocular Drug Delivery Implant. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5299.
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© ARVO (1962-2015); The Authors (2016-present)
To design a novel ring shaped device intended for implantation in the lens capsular bag at the time of cataract surgery.
To control the release of Avastin® we have investigated 3 commercially available hydrophilic and biocompatible membranes: Polyethersulfone (PES), Polycarbonate (PC), and Polyvinylidene Fluoride. The membrane is attached to a 1 - 4 mm2 hole that has been previously cut in a controlled drug delivery ring (CDR). An rhVEGF ELISA with known concentrations for calibration was used to assay samples collected. Side by side diffusion chambers of 2 ml each (donor and receiver) were used to identify the permeability coefficients of our Avastin® formulation for each membrane. 1 ml samples were taken from the receiver and replaced with an equal volume of fresh PVA every 2 to 6 hours for a maximum of 24 hours. We also conducted drug release studies using the PES and PC membranes to determine diffusion coefficients for later translation into a suitable in vivo Avastin® formulation. Samples were taken and replaced with an equal volume of fresh BSS daily for the first week and 1 - 2 times per week thereafter until no Avastin® was detected.
The CDR will provide long-term sustained release of drug from a 100 µl reservoir. One candidate drug that we are investigating is Avastin® which is currently administered via intravitreal (IV) injections at 1.25 mg/month. We have formulated Avastin® with a polyvinyl alcohol (PVA) polymer to increase Avastin® stability and slow the release rate from the CDR. CDRs were filled with 50 - 100 µl of 12.5 and 25 mg/ml Avastin® solutions and placed in 4 ml of balanced salt solution. We found continuous elution for >2 months and therefore the CDR is a plausible alternative to monthly IV injections.
In vitro diffusion studies confirm long-term release of Avastin® from the CDR.
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