Sequential multi-step flash nanoprecipitation for the formation of nanoparticles with high core loadings

Abstract

From diagnostic imaging to drug delivery, nanoparticles have found a tremendous variety of uses across fields. Often, when designing these nanoscale constructs, the two most important criteria are particle size and core loading. For example, small particles below 100 nm can have many advantages for drug delivery—including improved specificity to tumors through the enhanced permeability and retention (EPR) effect. Likewise, higher loading nanoparticles translate very well to more effective drug delivery and cancer imaging—allowing for lower dosage and reduced costs. Traditional formulations of nanoparticles using drug absorption or precipitation methods generally struggle to obtain >50% loading. Disclosed herein is a precipitation process allowing for production of stable particles at very high core loading by taking advantage of different time scales while maintaining biologically relevant sizes. New mixing designs allow for the separation of the precipitation and stabilization steps to generate these high loading nanoparticles.