Rapid diffusion of large polymeric nanoparticles in the mammalian brain

A dosage formulation for delivery of a therapeutic, prophylactic or diagnostic agent to the brain, the formulation consisting of

• a. polymeric nanoparticles having a diameter of at least about 40 nm and less than about 200 nm, the nanoparticles having a hydrophobic polymeric core and being coated with a hydrophilic polymer comprising polyalkylene oxide or a block copolymer containing polyalkylene oxide blocks, in an amount effective to result in a neutral or near neutral charged surface between −10 mV and 10 mV measured as zeta-potential in phosphate buffered solution, pH 7.0 using laser Doppler anemometry and having a number density of at least 0.1 hydrophilic polymer per nm2 of nanoparticle surface, wherein the hydrophilic polymer is present in a weight percent of greater than 80% relative to the total weight of the polymeric nanoparticles,
• b. an effective amount of a therapeutic, prophylactic or diagnostic agent to prevent or treat a disease or disorder of the brain, encapsulated in or on the nanoparticles, and
• c. a pharmaceutically acceptable excipient for delivery into the brain,
• wherein the nanoparticles have a diffusion rate at most about 60-fold slower in the brain than in water, whereas the same nanoparticles without the hydrophilic polymer coating have a diffusion rate at least about 16,000-fold slower in the brain than in water, characterized by measuring average effective diffusivities at a time scale of 1 second of respective nanoparticles in cortical tissue relative to in water (Dw/Db).