Highly-loaded protein nanocarriers prepared by Flash NanoPrecipitation with hydrophobic ion pairing

The efficient encapsulation of therapeutic proteins into delivery vehicles, particularly without loss of function, remains a significant research hurdle. Typical liposomal formulations achieve drug loadings on the order of 3–5% and encapsulation efficiencies around 50%. We demonstrate the encapsulation of model proteins with isoelectric points above and below pH 7 into nanocarriers (NCs) with protein loadings as high as 46% and encapsulation efficiencies above 95%. This is done by combining the continuous nanofabrication process Flash NanoPrecipitation (FNP) with the technique of hydrophobic ion pairing by forming and encapsulating an ionic complex within a nanocarrier stabilized by a block copolymer surface layer.