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S. A. Molokhia, H. J. Sant, M. C. Hanson, R. M. Burr, A. E. Poursaid, C. J. Bishop, J. M. Simonis, B. K. Gale, B. K. Ambati; New Intraocular Drug Delivery Device. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5974.
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© ARVO (1962-2015); The Authors (2016-present)
The objective was to develop a new sustained release, refillable intraocular drug delivery system that fits in the capsular lens for potential multi drug use. The approach is to have a capsule ring with a drug reservoir of 100µl volume that fits within the lens capsular bag and is inserted through a 2.75 mm wound (standard cataract incision size)
The capsule drug ring (CDR) prototypes were manufactured using computer numerical control machine (CNC, Haas Automation Inc., CA). The shell for the drug reservoir was made of PMMA (Perspex, Goodfellow Corporation, PA). A Perspex sheet of 2.0 mm thickness was used as the starting material. The preliminary check valves were made using a silicone elastomer (C6540, Dow Corning Corporation, MI) for a standard 27 gauge ophthalmic cannula to fill the reservoir. The CDR at this point has one face open for a semi permeable membrane to adhere on its surface. Passive permeability studies in vitro were performed in a side-by-side diffusion cell using hydrophilic or hydrophobic semi permeable membranes of different pore sizes and Avastin® as the drug of interest. The Avastin® samples were collected from the receiver compartment at predetermined time and assayed by an ELISA protocol. Polyvinyl alcohol (PVA) 87-89% hydrolyzed (molecular weight 146-158 kDa) of high viscosity was investigated as the drug carrier.
A circular ring shape prototype device was developed to maximize the volume available in the capsular bag and have a drug reservoir of 100µL. An early stage prototype CDR model was manufactured. Two valves are included in the design for potential use of multi-drug disease treatment. The semi permeable membranes showed a permeability coefficient value (P) in the order of 10-7 cm/sec. The smaller pore size membrane showed almost two-fold lower P value when compared to the larger pore size of the same semi permeable membrane. PVA had a viscosity value of approximately 50-times higher than Avastin® at a similar concentration (50 mg/ml) and a shear rate of 10 sec-1
The results demonstrate successful manufacturing of a PMMA shell device with a semi permeable membrane. This shows the potential of the CDR device as an implantable ocular device for drug delivery. The use of CE 25 nm along with the high viscosity PVA could provide a sustained release profile for Avastin®.
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