Large-Scale Synthesis of Lipid-Polymer Hybrid Nanoparticles Using a Multi-Inlet Vortex Reactor

Lipid polymer hybrid nanoparticles combine the advantages of both polymeric and liposomal drug carriers and have shown great promise as a controlled drug delivery platform. Herein, we demonstrate that it is possible to adapt a multi-inlet vortex reactor (MIVR) for use in the large-scale synthesis of these hybrid nanoparticles. Several parameters, including formulation, polymer concentration, and flow rate, are systematically varied, and the effects of each on nanoparticle properties are studied. Particles fabricated from this process display characteristics that are on par with those made on the lab-scale such as small size, low polydispersity, and excellent stability in both PBS and serum. Using this approach, production rates of greater than 10 g/h can readily be achieved, demonstrating that use of the MIVR is a viable method of producing hybrid nanoparticles in clinically relevant quantities.