INV-1028
Macrophages are important immune cells in the body that regulate different biological processes involved in inflammatory and infectious diseases. Macrophages originate from the mononuclear phagocyte system (MPS) in the bone marrow. The MPS system comprises of monocytes and tissue, it matures into a larger phagocytic cell called a macrophage. They reside in the liver (Kupffer cells), lungs, spleen, lymph nodes, thymus, gut. To combat inflammation and infections, macrophages have to be converted from the rested to an activated state. The activated cells have an enhanced capability to attack and kill infecting pathogens and tumor cells. The active state is marked by an increase in size and the development of more pseudopods. The cytokines released from T‑lymphocytes such as interferon‑gamma and granulocyte‑monocyte colony-stimulating factor can act as signals to activate macrophages. Additionally, the activating signal can come from microbial products such as lipopolysaccharides, immune complexes, chemical mediators, and extracellular matriculates proteins including fibronectin. Macrophages are capable of secreting various biological products, and if the process is left unchecked, it could result in tissue damage and fibrosis that are characteristic of chronic inflammation.
The delivery vehicles in this invention are specifically designed to have multi-compartments. The formulation can be designed to have solid hydrophilic or hydrophobic nanoparticles in a larger solid microsphere a) nanoparticles in water‑in‑oil‑in‑water multiple emulsions b) or nanoparticles or droplets in a gel. The construction of different constructs is based on the properties of the payload and the desired application of the system.
The nanoparticles and microparticles of the present invention can be modified for targeting macrophages using specific peptides (e.g. Tuftsin) surface functionalization. In addition, the inclusion of materials that promote pro- or anti-inflammatory properties (e.g., ovalbumin for pro-inflammation and immune-adjuvant response or omega-3 fatty acid-containing oils for anti-inflammatory response) can further enhance the therapeutic efficiency of the system.
This invention meet the needs of the payload (e.g., hydrophobic versus hydrophilic), the site of delivery in the body, the intended application (e.g., drugs versus vaccines), and the disease of interest.