Hybrid Milk Extracellular Vesicles as Potential Systems for Oral Delivery of siRNA

Abstract

Oral administration of RNA is currently not possible and current approaches for RNA delivery by injection are not suitable for the oral route. In this work, we report novel bioinspired nanoparticles for oral delivery of RNA therapies. Specifically, we report the fabrication of hybrid nanovesicles (“hybridosomes”) based on bovine milk extracellular vesicles (mEVs) and liposomes. Hybridosomes were fabricated using two related methods based on freeze‐thawing of mEVs and cationic liposomes. The systems were 180–230 nm and demonstrated efficient loading of siRNA cargo. Hybridosomes exhibited significantly lower cytotoxicity in intestinal Caco‐2 cells compared to cationic liposomes and superior stability in a fed‐state simulated intestinal fluid compared to liposomes. Furthermore, these systems significantly increased the transport of siRNA across in vitro intestinal model. Finally, hybridosomes loaded with siRNA successfully induced transfection in J774A.1 macrophages. Overall, our results show that the hybrid systems fabricated here offer potential for oral delivery of RNA therapeutics.This article is protected by copyright. All rights reserved