ABSTRACT
Pharmacotherapy is under continuous evolution towards the synthesis of more potent drug molecules against diseases. Unfortunately, the clinical effi cacy of such agents is considerably hampered by a nonspecifi c biodistribution that makes it diffi cult to accumulate the drug at the targeted site in therapeutic concentrations. Very frequently, poor pharmacokinetics (i.e., rapid metabolism and plasma clearance) and drug resistance mechanisms at the tissue and/or cellular level further contribute to pharmacotherapy failure (Arias 2009; Lammers et al. 2010). Poor biodistribution and lack of specifi city for non-healthy tissues and organs are also very important limitations to the use of contrast agents [e.g., magnetic resonance imaging (MRI) probes, luminophores, or radionuclides] for diagnostic purposes (Lu et al. 2007; Arias 2010). The unfavorable physicochemical properties of drug and contrast agents (i.e., hydrophobicity and high electrical charge) further explain the low accumulation of these molecules at the non-healthy cellular and tissular level (Couvreur and Vauthier 2006; Arias 2010). As a result, many of these agents that have been shown to be highly effective in vitro not only are ineffective in vivo but also exhibit toxicity.
