Co-encapsulation by Flash NanoPrecipitation of Insulin, Trypsin Inhibitor and Caprate Permeabilization Enhancer for Oral Administration

Abstract

We describe inverse-Flash NanoPrecipitation as a new scalable platform for co-encapsulation of insulin (a model therapeutic peptide) with soybean trypsin inhibitor (a peptidase inhibitor) and sodium caprate (a penneation enhancer) forming 300 nin particles for oral delivery. The co-encapsulation of the protein therapeutic with a protease inhibitor and a permeation enhancer into nanoparticles addr esses enzymatic attack on the protein dntg and the transport across the gastrointestinal tract barrier. Inverse-Flash NanoPrecipitation (iFNP) encompasses two sequential precipitation processes. First, insulin, soybean trypsin inhibitor (SBTI), and hydroxypropyl methylcellulose acetate-succinate polymer (HPMCAS, a stabilizing block co-polymer)(at mass ratios of 1:4:5) are rapidly precipitated into an organic antisolvent forming the inverted nano-core (iNC) with 50 wt% insulin and SBTI. Encapsulation efficiencies are greater than 98%. The second step involves the precipitation of sodium caprate and a stabilizing polymer coating onto the iNCs surface. HPMCAS, chitosan, and PEG polymers are used to coat the iNCs to generate nanoparticles with anionic, cationic, and neutral surfaces, respectively. This demonstrates that the iFNP platform can encapsulate complex biologies mixtures at high loadings into particles with customizable surface properties.