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We reported the development of multifunctional poly (lactic-co-glycolic acid) (PLGA)-lecithin-polyethylene glycol (PEG) core-shell nanoparticles (NPs) that combined the beneficial properties of liposome and polymeric NPs for chemotherapeutics delivery. The particle size, surface charge and surface functional groups were easily tunable in highly reproducible manner by various formulation parameters such as lipid/polymer, 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-PEG-COOH/lecithin, DSPE-PEG-COOH/DSPE-PEG-NH2 mass ratio and modification of terminal groups of DSPE-PEG. We encapsulated model chemotherapy drug, hydrophilic cisplatin (DDP) or hydrophobic DDP prodrug, in the NPs and showed high encapsulation efficiency, excellent stability, specific FA targeting recognition for MCF-7 cells with over FA receptors expression and pretty cytotoxicity. Such PLGA–lecithin–PEG core-shell nanoparticles (NPs) were proved to be a promising drug delivery nanocarrier for cancer-targeted therapy.
Since the discovery of cisplatin, drugs based on platinum, have made a significant impact on the treatment of various cancers. The administration of platinum drugs is however accompanied by significant side effects. This chapter discusses the types of drug delivery systems that have been developed in order to enable the targeted delivery while maintaining controlled temporal supply of the drug. The sizes of carriers range from nanometer to micrometer sized particles. The most common types of drug carriers are micelles, liposomes, nanoparticles, and dendrimers, but also a few microspheres have been developed. Most striking aspect of the delivery of platinum drugs is the possibility of physical encapsulation but also the binding of the drug to the polymer carrier coordinate covalent bond. Since platinum drugs have typically two permanent and two leaving ligands, the polymer can be part of either ligand. As the leaving ligand, the platinum drug is released often as cisplatin. If the polymer provides the functionality for the permanent ligand, a new macromolecular drug has been formed. In addition to the attachment of pt(II) drugs, recent offorts are devoted to the conjugation via the Pt((IV) prodrug.
Platinum-based drugs continue being the support of therapy for many different kinds of cancer. Cancer patients often present irreversible resistance to platinum after repeated treatment in clinic. Despite of the great efforts, chemoresistance (intrinsic or acquired) already is a major limitation in the management of this disease. In this review, the last current research on cancer characteristic and cancer chemical resistance is summarized, the major and novel strategies to reverse resistance to platinum- based drugs are discussed and this article mainly emphasizes the contribution of nanotechnology and combination therapies to target sites and reduce the cancer chemoresistance.