Engineering of polymer-stabilized nanoparticles for drugs with Log P values below 6 by controlled antisolvent precipitation

摘要

The present invention provides organic nanoparticles that include a molecule having a Log P value of about 3 or above, an amphiphilic diblock copolymer or a surfactant, and a pharmaceutically-acceptable hydrophilic polymer. The present invention also provides methods of making these nanoparticles, e.g., by flash nanoprecipitation, with control over particle size and surface properties. The methods of the present invention provide a means for co-precipitating a water-insoluble compound with an amphiphilic stabilizer within a few milliseconds. The nanoparticles of the present invention exhibit high drug loading, e.g., 50% w/w, and can be produced with a mean particle size less than 200 nm and with a narrow particle size distribution.