ABSTRACT
Many small and macromolecular therapeutics fail to treat diseases because of anatomical and physiological barriers that limit their direct entry into the target extracellular or intracellular compartments.1,2 The major hurdles for these therapeutic molecules reaching the target compartment are poor aqueous solubility, permeability, stability, and limited transport across epithelial layers in the biological environment.1 These problems are particularly signicant in the case of macromolecular therapeutic agents such as nucleic acids (plasmid DNA, oligonucleotides, small interfering doublestranded RNA), peptides, and proteins.
