Poor bioavailability and poor pharmacokinetic characteristics are some of the leading causes of drug development failure.
Therefore, poorly-soluble drugs, fragile proteins or nucleic acid products may benefit from their encapsulation in nanosized vehicles,
providing enhanced solubilization, protection against degradation, and increased access to pathological compartments. A key element for
the success of drug-loaded nanocarriers is their ability to either cross biological barriers themselves, or allow loaded drugs to traverse
them to achieve optimal pharmacological action at pathological sites. Depending on the mode of administration, nanocarriers may have to
cross different physiological barriers in their journey towards their target.
In this review, the crossing of biological barriers by passive targeting strategies will be presented for intravenous delivery (vascular
endothelial lining, particularly for tumor vasculature and blood brain barrier targeting), oral administration (gastrointestinal lining), and
upper airway administration (pulmonary epithelium). For each specific barrier, background information will be provided on the structure
and biology of the tissues involved as well as available pathways for nano-objects or loaded drugs (diffusion and convection through
fenestration, transcytosis, tight junction crossing, etc.). The determinants of passive targeting − size, shape, surface chemistry, surface
patterning of nanovectors − will be discussed in light of current results. Perspectives on each mode of administration will be presented.
The focus will be on polymeric nanoparticles and dendrimers, although advances in liposome technology will be also reported as they
represent the largest body in the drug delivery literature.