ABSTRACT
In order to increase the therapeutic ef‡cacy of a drug or to reduce its toxicity, biodistribution and intracellular traf‡c have to be changed, since the sole modi‡cation of its pharmacokinetics is insuf‡cient. Nanomedicines (nano-objects loaded with small drugs or macromolecules) are powerful tools developed in the framework of the application of nanotechnology to medicine1 that, functioning as nano-drug delivery systems, are capable of modifying the pathway followed by molecules.2-5 Pharmacokinetics, biodistribution, and intracellular traf‡c of loaded molecules no longer depend on their chemical structures but on the size, shape, and chemical structure of the nano-object.6 Liposomes, for instance, are the best known example of nano-objects, recently clasi‡ed as nanoparticules (with their three dimensions in the nanoscale (<200-300 nm)).7 Different from conventional drug delivery systems, and depending on the biodegradability of the nanoobject, nanomedicines can cross anatomical and phenomenological barriers.8,9 They can be administered by parenteral, transcutaneous, or mucosal vias,10 but changes in biodistribution can only be achieved upon parenteral administration11-22 (Figure 20.1). An exclusive feature of nanomedicines is their uptake by phagocytic or pynocitic mechanisms upon cell recognition.23,24 The structure of the nanomedicine is responsible for its own recognition by a given mechanism of cellular uptake.25 Each uptake mechanism leads to well-de‡ned intracellular traf‡c mediated by vesicles, which ends up in different cellular compartments26 (Figure 20.2).
