Nanoparticles can serve a number of roles in drug delivery depending on the therapeutic molecule and mechanism of delivery. Orally delivered nanoparticles loaded with poorly soluble drugs can enhance dissolution rates and improve bioavailability. Conversely, parenterally delivered nanoparticles loaded with poorly soluble drugs may be used to slow release and better localize the therapeutics to tissues of interest. For parenteral administration of water soluble drugs (particularly biologics such as peptides, proteins, and nucleic acids), nanoparticle delivery vehicles can allow for reduced immune recognition, longer clearance times, reduced frequency of injections, and enhanced intracellular delivery. Independent of the drug or application, the nanoparticles need to be made with high loadings and encapsulation efficiencies in a reproducible and scalable process.<br/><br/>Here, the Flash NanoPrecipitation (FNP) process is described. In FNP, a drug and stabilizing polymer are dissolved in a solvent stream which is rapidly mixed with a non-solvent stream in specially-designed mixing geometries. The non-solvent causes the diffusion-limited growth of the nanoparticle core, which is halted by the self-assembly of the stabilizing polymer on the nanoparticle surface. This process can be run at a ~5 mL lab bench scale to a ~L/min industrial scale. Starting with hydrophobic compounds in which an aqueous anti-solvent is employed, we discuss the rules for controlling nanoparticle size and surface characteristics. Next, for weakly hydrophobic compounds, we describe the formation of prodrugs or insoluble salts to enable encapsulation. Finally, for water soluble compounds, the inverse FNP (iFNP) process is described. In iFNP a nonpolar antisolvent is used, resulting a nanoparticles with a hydrophilic core and hydrophobic corona. The iFNP process has led to delivery vehicles with unprecedented loadings (up to 50%) and encapsulation efficiencies (up to 99%).

Flash nanoprecipitation for drug delivery applications: From hydrophobic small molecules to hydrophilic macromolecules

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.