When carrier-mediated systems containing multiple drugs come to fruition as novel drug delivery systems in general cancer therapy it can also be adapted to metastatic breast cancer treatment, which requires aggressive therapy. Widely investigated carriers for multiple drug delivery such as liposomes, dendrimers, polymeric nanoparticles, and water-soluble polymer-drug conjugates Inhibitors,research,lifescience,medical are reviewed below. 4.1. Combination Drug Delivery Systems Based on inhibitors liposomes Liposomes are spherical vesicles composed of one or more

lipid bilayers with a drug containing aqueous core (Figure 2(a)). Liposomes are one of the most widely used pharmaceutical carriers with several unique characteristics such as (1) ability to encapsulate both hydrophilic and hydrophobic drugs and (2) protecting the encapsulated drugs

from the external environment [64]. Unmodified liposomes are rapidly cleared from the blood by phagocytic cells of the reticuloendothelial Inhibitors,research,lifescience,medical system (RES), resulting in premature degradation and systemic clearance Inhibitors,research,lifescience,medical [64]. To overcome this challenge long-circulating stealth liposomes have been developed by coating the surface with an inert and biocompatible polymer such as polyethylene glycol (PEG). The polymer layer provides a protective shell over the liposome surface and suppresses liposome recognition by opsonins, and therefore prevents rapid clearance by the RES [65]. Several examples of combination drug delivery systems based on liposomes are listed in Table 3. Zucker et al. has developed a Inhibitors,research,lifescience,medical PEGylated nanoliposome

(LipoViTo) for simultaneous delivery of two chemotherapeutic agents (topotecan and vincristine) [66]. In mice xenograft studies, the simultaneous delivery of two agents by the LipoViTo system altered the biodistribution of each individual drug in favor of the tumor resulting in >100-fold higher tumor levels. This ultimately resulted in a higher Inhibitors,research,lifescience,medical therapeutic response (91% tumor suppression) from the dual-drug liposome formulation, which could not be achieved by either administering a combination of free drugs Parvulin (29% tumor suppression) or liposomal formulations containing only one drug (38–43%). Figure 2 Combination drug delivery systems based on liposomes. (a) Combination of drugs encapsulated in the hydrophilic core of liposome (b) polymer-caged nanobin (PCN); liposome-based hybrid system carrying a combination of encapsulated drug and conjugated drug. … Table 3 Combination drug delivery systems based on liposomes. Another unique liposomal system is a polymer-caged nanobin (PCN, Figure 2(b)) developed by Lee et al., which illustrates the different ways to incorporate multiple drugs in the same liposome such as encapsulation of one drug and covalent conjugation of the other.