Targeted Theragnostic Nanoparticles Via Flash Nanoprecipitation: Principles of Material Selection
Flash NanoPrecipitation is a simple, rapid, and scalable method capable of continuously processing nanoparticles with sizes tunable between 50 and 500 nm with narrow size distributions and high drug loading capacities. In Flash NanoPrecipitation, an amphi
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Targeted Theragnostic Nanoparticles Via Flash Nanoprecipitation: Principles of Material Selection Christina Tang and Robert K. Prud’homme
Abstract Flash NanoPrecipitation is a simple, rapid, and scalable method capable of continuously processing nanoparticles with sizes tunable between 50 and 500 nm with narrow size distributions and high drug loading capacities. In Flash NanoPrecipitation, an amphiphilic block copolymer is dissolved in organic solvent with a desired core material. When rapidly mixed with a miscible antisolvent for the core material that causes a rapid decrease in solvent quality, the core material precipitates and the amphiphilic block copolymer self-assembles directing the formation of a colloidal nanoparticle. Adsorption of the hydrophobic block of the block copolymer arrests precipitation of the core material and the hydrophilic block sterically stabilizes the nanoparticle. The assembled nanoparticles are kinetically frozen. Given appropriate mixing conditions (i.e., time scales of mixing faster than nanoparticle formation), the rate of nucleation and growth of the precipitating core material must be appropriately matched with the rate of self-assembly. This bottom-up approach can be adapted to multiple systems of interest and can be used to encapsulate hydrophobic drugs and/or imaging agents. Methods to encapsulate a range of materials including poorly water soluble drugs [active pharmaceutical ingredients (APIs)], weakly hydrophobic, ionizable APIs as well as peptides, siRNA, organic, and inorganic imaging agents have been developed. Multiple components (drugs and/or imaging agents) can be coprecipitated to develop multifunctional nanoparticles with therapeutic and diagnostic capabilities. Further, the surface chemistry of the nanoparticle can be tailored to enable active targeting. To control the surface chemistry, a functionalized block copolymer can be incorporated into the mixing/assembly process. The functionalized block copolymer can be the block copolymer conjugated to a small molecule targeting ligand (e.g., mannose, folate). Alternatively, the PEG end of the block copolymer can be modified with a reactive end group for conjugation to a targeting ligand after the nanoparticle has been assembled. Surface modifications with small molecules, single stranded DNA, peptides, and proteins have been performed. Appropriate material selection is C. Tang R.K. Prud’homme (&) Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA e-mail: [email protected] © Springer International Publishing Switzerland 2016 C. Vauthier and G. Ponchel (eds.), Polymer Nanoparticles for Nanomedicines, DOI 10.1007/978-3-319-41421-8_3
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critical in the formulation of functional and stable nanoparticles dictated by choice of the core material and stabilizer, respectively. Therefore, we review examples of how Flash NanoPrecipitation has been used to formulate nanoparticles for potential applications in targeted delivery of cancer therap
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