Formation of nanoparticles for the oral delivery of small molecules by Flash Nanoprecipitation

Nanoparticles have shown considerable potential in many biological applications including drug delivery, bio-imaging, and medical diagnostics. Specifically, the development of nanoparticle-based drug formulations holds opportunities to improve the dissolution rate and oral availability of poorly water-soluble drugs. The goal of this project is to improve oral bioavailability of a small molecule drug (“G-1”) through the formation of nanoparticles using the flash nanoprecipitation (FNP) process. Interestingly, “G-1” formed ~80 nm particles that are electrostatically stabilized without the use of stabilizing polymers and concentration as high as 160 mg/mL of “G-1” formed nanoparticles. Additionally, trehalose was found to be an effective cryoprotectant for lyophilization of “G-1” nanoparticles suspension into stable dried powders. Unexpectedly, the release kinetics of “G-1” in its free powder form exhibit rapid dissolution rate in the modified biorelevant media (FaSSIF with 1.5% Tween 20). Further formulations with “G-1” were conducted to generate ~300 nm particles with PS-b-PEG as stabilizing polymer. Through the use of a tangential flow filtration (TFF) system, drug loading (wt%) of the lyophilized “G-1” nanoparticles were increased by nearly 2-fold (30.5% versus 16.7%). These lyophilized nanoparticles were introduced to Genentech’s in vivo and in vitro studies and have provided more insight in the bioavailability and pharmacokinetics properties of this drug.