Retinal Drug Delivery System

Development of a Novel Prescriptive Retinal Drug Delivery System using TheriFormtm Technology: Therics has designed a "prescriptive" retinal implant system to treat traction retinal detachment induced by leukocyte proliferation. The dosage form will pulse 4x4 mg doses of 5-FU, each at 4 day intervals. The hypothesis is that pulsatile delivery will be more efficacious than continuous release of the antiproliferative agent because it will effectively circumvent the P-Glycoprotein efflux system which leads to multiple drug resistance. Alternatively, the dosage form could also release a non-steroidal anti-inflammatory agent, diclofenac, alone or in combination with 5-FU, at an average rate of 80 micrograms a day to minimize pain and inflammation. The multicompartmental multidrug implant will be constructed employing Therics' proprietary 3-dimensional fabrication technology, TheriForm. This unique process will build the microarchitecture layer-by-layer by printing polymer binder onto a polyester powder bed which forms the fundamental backbone of the system. Various polymers will be introduced at selected points to form erosion layers which control delay time through varying composition and thickness. This Phase I Proposal describes the prototypic design strategy and outlines laboratory experiments which will characterize release rates of the two agents, as well as determine the physical/mechanical properties of the bicerodible implant, both during and after release. Therics will then be positioned to aseptically fabricate supplies suitable for animal studies. Developing this product will serve as the platform, not only for an ophthalmic family of retinal implants, but also for a number of other delivery Systems where pulsatile release is indicated. Of particular interest to the DoD might be vaccines where a delayed booster shot would be automatically released in the field, or perhaps subcutaneous implants for chronic treatment such as malarial suppression therapy