This study focuses on the design, simulation, and development

of an implantable ocular drug delivery device. A novel design concept consisting of micro/nanochannels embedded between top and bottom covers with a drug mostly reservoir made from PDMS material was developed. Several simulations were carried out with different microchannel configurations in order to see the feasibility for ocular drug delivery applications. Finally, a prototype illustrating the three components of the drug delivery design is presented. 2. Design and Development 2.1. Device Concept A novel implantable device incorporating nano-/microchannels is proposed for ocular drug Inhibitors,research,lifescience,medical delivery. As shown in Figure 1, the drug is stored in a reservoir at one end of the device. Microchannels are coated with hydrophilic coatings so that the drug from the reservoir diffuses through the channels at specified/designed rate into the eye eliminating the need for any controlled actuation. Hydrogels (MIRAgel, MIRA Inc, Waltham, Mass), consisting Inhibitors,research,lifescience,medical of poly (methyl acrylate-Co-2-Hydroxyethyl acrylyte) are used as

means to passively induce the drug delivery into the microchannels so that the drug diffuses freely through the channels and reaches Inhibitors,research,lifescience,medical the outlet for delivery. The microchannel component with inlet/outlet reservoirs will be enclosed in a PDMS case whose base is rounded to match the curvature of the eye globe. The device is attached securely to the sclera of the eye Inhibitors,research,lifescience,medical with fine 10–0 or 9–0 nylon sutures. Ideally, the device would be surgically, transclerally implanted in the vitreous space with an external thin curved spherical surface

flange that would be nearly flush with the sclera and sutured in place (see Figure 2). The design requirements for the proposed drug delivery device are as follows: target overall volume is less than 280mm3; diffusion rate is less than 0.07nL/min; target diffusion time period will be around 1 to 2 years; kinetics: reliable diffusion coefficient of drugs through the microchannels; implantable: eliminate repeated injections for effective treatment; actuation: Inhibitors,research,lifescience,medical sustained release drug delivery methods. Figure 1 Proposed device design concept for ocular drug delivery. Figure 2 An overview of the attachment Dacomitinib of the implanted drug delivery device to the eye. 2.2. Design Calculations To illustrate the targeted volume and rate of the drug delivery device, the following section provides the details of calculations. It has been assumed that drug-contained deionized water will be transported through the microchannel from a reservoir. The Ivacaftor FDA corticosteroid fluocinolone acetonide has low solubility, so that solution was made by dissolving 59mg of C24H30F2O6 in deionized water of 50μL (concentration in the device ≈ 1.18mg/μL). We also assume that the concentration of drugs in the water within the reservoir is around 1.18mg/cm3 and zero concentration within the retina region of the eye.