Mass Transport via Cellular Barriers and Endocytosis - Intracellular Delivery: Fundamentals and Applications - page 9

Fig. 2 Specialized transport systems for drugs and endogenous substances (Reprinted from
Giacomini et al. ( 2010 ). Courtesy of Nature Publishing Group)

2.1.3 Paracellular Transport

Paracellular transport is defined as the pathway along the water-filled tight junctions
between adjacent cells. Tight junctions normally regulate the trafficking of nutri-
ents, fluids and small molecules, with a cut-off of 500 Da (Siccardi et al. 2005 ; Gad
2008 ). This type of transport occurs through diffusion and based on its aqueous
nature, it is most relevant for small hydrophilic drugs that cannot penetrate cell
membranes (Nellans 1991 ; Karlsson et al. 1999 ).

2.2 Intravenous Administration: Endothelial Barriers

The delivery of therapeutic agents to a target site after systemic administration
involves three processes which all require bypassing biological barriers: distribu-
tion through vascular compartments, extravasation and transport in the interstitium
(Au et al. 2001 ; Ferrari 2010 ). These processes are influenced by the physico-
chemical properties of the drug, including size, surface charge, surface flexibility,
and binding with extracellular and intracellular macromolecules, as well as the
physiological properties of the targeted site, which, in the case of cancer, includes