Executive Summary : | Osteoarthritis (OA), a painful and debilitating condition affecting over 10 million people in India, has been managed with pain medication, viscosupplements, and surgery. Recent studies have shown the involvement of pro-inflammatory cytokines and immunomodulatory drugs in disease pathology. However, many disease-modifying osteoarthritic drugs (DMOAD) and anti-inflammatory molecules have poor water solubility, low bioavailability, and off-target localization associated toxicities, which limit their usage. To address these challenges, researchers plan to use two types of virus-like particles (VLPs) to address targeted drug delivery in OA. The first type is based on the capsid of an insect virus, Flock House Virus (FHV), which can be chemically conjugated with targeting peptides for specific tissue localization properties. The second type mimics Chikungunya Virus (CHIKV) particles, which localize to chondrocyte, synoviocyte, and FLS cells in joints. A detergent-based transient destabilization strategy will be used to package foreign molecules inside CHIKV VLP envelopes. The ability of the particles to release drugs will be tested in Fibroblast-like synoviocytes (FLS) and chondrocytes in culture, and the effect of the released drugs on inflammatory cytokine, growth factor, and angiogenesis marker expression will be analyzed. For further testing, a unique 3D bioprinted osteo-chondral tissue model will be developed from silk fibroin bioink, seeded with patients' chondrocytes and osteoblasts, and an in vitro OA disease model system will be established. Drug-loaded engineered VLPs will be tested in this close-to-authentic OA microenvironment, with the hope of establishing them as effective nanocarriers targeting arthritic tissues with strong commercial prospects. |