Barriers to in vivo nanoparticle
delivery following intravascular
administration. For nanoparticles to successfully reach their targets,
they must pass several barriers. This example uses intravascular administration
as a case study; other routes of administration are reviewed elsewhere.10−17 Unless immune responses are specifically desired, the nanoparticles
must evade recognition by the innate and adaptive immune system during
circulation (e.g., the complement system, the mononuclear phagocytic
system (MPS), and B cells). Once near the target organ, they must
travel past endothelial cells and tight junctions, which line blood
vessels. Then the nanoparticles must travel through extracellular
matrices within the target tissue, and once they reach the target
cells, must access their intended subcellular compartment for therapeutic
payload delivery. Reprinted with permission.(8)