Targeted delivery of drugs to macrophages has attracted considerable attention in developing new therapeutic modalities for chronic inflammatory disease. In this study, folic acid is covalently bound with chitosan (CS), using polyethylene glycol (PEG) as a spacer, for the preparation of CS-PEG-FA conjugates with prominent targeting moieties capable of specific interaction with the folate receptors (FR) on macrophages. In the study, average particle size, light scattering intensity and zeta potential of the self-assembled CS-PEG-FA/HA nanoparticles are all determined by dynamic light scattering particle size analysis (DLS). Reactive oxygen species (ROS) secreted by activated macrophages play a important role in causing rheumatoid arthritis, and therapeutics that can inhibit the production of ROS by macrophages have great clinical potential. Superoxide dismutase (SOD) and catalase (CAT) are two enzymes that scavenge ROS and have great potential for treating rheumatoid arthritis. In this study, we will demonstrate that CAT and SOD encapsulated in the nanoparticles can be effectively targeted to activated macrophages, via the folate receptor. The enhanced uptake of enzyme-incorporated nanoparticles into activated macrophages and their ability to scavenge ROS, produced by the macrophages, will be studied by cell culture experiments. Hydrocyanine can be incorporated in the nanoparticles for targeting macrophages to detect various ROS including superoxide anion and hydroxyl radical generated in an inflammatory macrophage. The CS-PEG-FA/HA nanoparticles can also be used for encapsulating photosensitizers and become excellent drug-delivery systems for the selective delivery of a photosensitizers, Chlorin e6 (Ce6), to macrophages and photodynamic destruction of these cells for the inhibition of inflammatory responses.
|Effective start/end date||8/1/13 → 7/31/14|