ABSTRACT
The low oral bioavailability of some drugs is clearly a limitation to their development as a medicine. Transport mechanisms across the intestinal barrier are numerous and vary greatly depending on the physicochemical properties of a given substance. Depending on the molecule, inefficient oral delivery may result from several mechanisms. Indeed, the drug may be unstable in the gastrointestinal (GI) tract, which is very rich in ubiquitous enzymes with a wide array of activity. On the other hand, the intestinal epithelium represents a rather impermeable barrier. Only small molecules can cross the intestinal barrier via the paracellular route. For other drugs not using existing receptors or receptor-like transport, it is necessary to have the perfect partition coefficient to be able to pass through the bilipidic layer of the cell membrane and still be able to stay dissolved in the hydrophilic environment of extracellular and cytosolic environments. Thus, basically, very hydrophilic or lipophilic drugs are unable to cross the intestinal barrier. Furthermore, after absorption, drugs may also suffer from a significant hepatic first pass, fast elimination, or unwanted large distribution. For these drugs, encapsulation in polymeric particles may offer several advantages by isolating the molecule from the external milieu, promoting absorption, and providing a controlled release and/or a targetable system.Moreover, encapsulation will decrease adverse effects, in particular, of irritating compounds by preventing contact with the mucosal wall.
