Lens Capsule Based Extended Drug Delivery Device

PROJECT SUMMARY/ABSTRACT Noninfectious uveitis is often managed using systemic medications or steroids. Both have undesirable side effects. Local steroid side effects include elevated intraocular pressure, potentially requiring surgery, and cataract formation. Systemic immune suppression has side effects that include end organ damage, certain malignancies, and susceptibility to opportunistic infections. The long term research goal of this proposal is to develop viable long term treatments for ocular inflammation using extended intraocular delivery of biologics and immune modulating peptides. This aligns with the NEI priority to develop steroid therapy alternatives for ocular inflammation without side effects such as cataracts or glaucoma. The objective of this proposal is to develop a refillable micromachined lens capsule based drug reservoir for delivery of adalimumab via diffusion and a novel immune modulating peptide using an encapsulated cell-based therapy. The central hypothesis is that a lens capsule based drug reservoir will be able to safely allow extended pharmaceutical delivery to the anterior and posterior segment of the eye. The rationale underlying this proposal is that completion will identify a new technique of locally delivering non-steroidal based therapies for noninfectious uveitis, allowing localized long term immune modulation with a more favorable side effect profile than current therapies. The central hypothesis will be tested by pursuing two specific aims: 1) characterize and control the release of adalimumab from an engineered lens capsule delivery device in vitro and in vivo; 2) characterize and control cell-based production and release of an immune modulating peptide biopharmaceutical from within an engineered lens capsule delivery device in vitro and in vivo. These two aims will be evaluated using an innovative approach using a microfabricated, collapsible, and refillable intraocular drug delivery device implanted into the lens capsule capable of delivering biologics via diffusion and peptide molecules through cell-based production. Characterization will occur on the benchtop and after implantation into a rabbit model. The proposed research is significant because it has the potential to provide new therapies for ocular inflammation in noninfectious uveitis and may open new avenues for managing other chronic ocular diseases. The expected outcome of this work is an improved understanding of how intraocular cell-based and diffusion based therapies can deliver pharmaceuticals in ocular inflammation. These results will have an important and immediate positive impact because they will establish a new way of treating ocular inflammation locally with extended biologic and peptide delivery without the side effect profile of steroids. The findings of this study will provide the framework for an R01 grant with long term animal implantation testing and will prepare for human clinical testing. This work will help to ultimately determine whether localized continuous biologic and peptide drug delivery can provide improved clinical outcomes.