Immune-modifying nanoparticles for the treatment of inflammatory diseases

Abstract

The current invention involves the administration of negatively charged particles, such as polystyrene, PLGA, or diamond particles, to subjects to ameliorate inflammatory immune responses. Additionally, the present invention describes methods of treating inflammatory diseases by administering these same negatively charged particles.

1 . A method of ameliorating inflammatory response in a subject in need thereof, comprising: administering to the subject an effective amount of a composition comprising negatively charged particles having a zeta potential of about −100 mV to about −30 mV, wherein the particles do not comprise one or more therapeutically active agents. 
     
     
         2 . The method of  claim 1 , wherein the negatively charged particles comprise one or more carboxyl groups on the particle's surface. 
     
     
         3 . The method of  claim 1 , wherein the negatively charged particles have a zeta potential of about −75 mV to about −30 mV. 
     
     
         4 . The method of  claim 1 , wherein the negatively charged particles have a zeta potential of about −60 mV to about −30 mV. 
     
     
         5 . The method of  claim 1 , wherein the negatively charged particles have a zeta potential of about −50 mV to −30 mV. 
     
     
         6 . The method of  claim 1 , wherein the negatively charged particles comprise polyglycolic acid (PGA), polylactic acid (PLA), polystyrene particles, poly (lactic-co-glycolic acid) (PLGA), polyanhydride, or a combination thereof. 
     
     
         7 . The method of  claim 1 , wherein the negatively charged particles comprise PLA. 
     
     
         8 . The method of  claim 1 , wherein the negatively charged particles comprise PGA. 
     
     
         9 . The method of  claim 1 , wherein the negatively charged particles comprise PLGA. 
     
     
         10 . The method of  claim 9 , wherein the PLGA comprise about 10:90, about 20:80, about 50:50, about 80:20, or about 90:10 PGA:PLA. 
     
     
         11 . The method of  claim 9 , wherein the PLGA comprise about 50:50 PGA:PLA. 
     
     
         12 . The method of  claim 1 , wherein the diameter of the negatively charged particles is about 0.1 μm to about 10 μm. 
     
     
         13 . The method of  claim 1 , wherein the diameter of the negatively charged particles is about 0.1 μm to about 5 μm. 
     
     
         14 . The method of  claim 1 , wherein the diameter of the negatively charged particles is about 0.1 μm to about 3 μm. 
     
     
         15 . The method of  claim 1 , wherein the diameter of the negatively charged particles is about 0.1 μm to about 1 μm. 
     
     
         16 . The method of  claim 1 , wherein the diameter of the negatively charged particles is about 0.1 μm to about 0.5 μm. 
     
     
         17 . The method of  claim 1  wherein the composition is administered orally, nasally, intravenously, intramuscularly, ocularly, transdermally, intraperitoneally, or subcutaneously. 
     
     
         18 . The method of  claim 17 , wherein the composition is administered intravenously. 
     
     
         19 . The method of  claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier or excipient. 
     
     
         20 . The method of  claim 1 , wherein administering the negatively charged particles reduces pro-inflammatory mediators from an inflammatory milieu in the subject. 
     
     
         21 . The method of  claim 1 , wherein administering the negatively charged particles induces monocyte and/or neutrophil apoptosis in the subject. 
     
     
         22 . The method of  claim 1 , wherein the subject in need thereof has a brain injury, a spinal cord injury, an autoimmune disorder, an allergic disorder, a concussion, an empyema, a post-traumatic stress disorder, a soft tissue injury, a wound, an ischemic reperfusion injury, atherosclerosis, a viral infection, or a bacterial infection. 
     
     
         23 . The method of  claim 22 , wherein the autoimmune disorder is selected from the group consisting of multiple sclerosis, scleroderma, type-I diabetes, rheumatoid arthritis, thyroiditis, systemic lupus erythematosus, Reynaud's syndrome, Sjorgen's syndrome, autoimmune uveitis, autoimmune myocarditis, inflammatory bowel disease, amyotrophic lateral sclerosis, psoriasis, celiac disease, ulcerative colitis, and Crohn's disease. 
     
     
         24 . The method of  claim 22 , wherein the allergic disorder is eczema, asthma, allergic rhinitis, dermatitis, or skin hypersensitivity. 
     
     
         25 . The method of  claim 22 , wherein the viral infection is a herpes virus infection, a hepatitis virus infection, a West Nile virus infection, a flavivirus, an influenza infection, a rhinovirus infection, a papillomavirus infection, or parainfluenza virus infection. 
     
     
         26 . The method of  claim 22 , wherein the bacterial or viral infection infects the central nervous system of the subject and causes encephalitis or meningitis. 
     
     
         27 . The method of  claim 22 , wherein the bacterial infection causes sepsis. 
     
     
         28 . The method of  claim 1 , wherein the subject in need thereof has a myocardial infarction. 
     
     
         29 . The method of  claim 1 , wherein the subject in need thereof has a brain injury or spinal cord injury. 
     
     
         30 . The method of  claim 1 , wherein about 10 3  to about 10 15  particles are administered to the subject.