ABSTRACT
Thanks to the deep investigation into the biology and physiology of cancer, numerous molecular targets have been identifi ed for chemotherapy. Recent investigations have led to the design of novel molecules with greater antitumor activity compared to traditional anticancer agents. On the contrary, the clinical use of such drugs does not offer signifi cant possibilities over the (frequently limited) conventional chemotherapy. This is clearly the consequence of an insuffi cient accumulation of the drug into the targeted site in optimal quantities and/or an ineffi cient anticancer activity. Hence, treatment failure can occur in sensitive cancers even if more advanced chemotherapy schedules are used. It has been described that the unfavourable pharmacokinetics and poor physicochemical properties of these molecules (i.e., hydrophobicity) dramatically contribute to the problem, and limit their clinical use. For instance, antitumor drugs are characterized by a short plasma half life (t1/2) due to a very rapid plasma clearance and biodegradation. Additionally, poor tumor selectivity and large biodistribution (inducing severe toxicity in healthy tissues) frequently come across. Last but not least, these agents are sensitive to enzymatic systems, and are supposed to induce drug resistance in cancer cells. For that reason, highly toxic doses and rigorous treatment schedules are normally used to obtain the therapeutic effect (Brigger et al. 2002; Arias 2009).
