Clinical application of anticancer drugs is limited by problems such as low water solubility, lack of tissue-specificity and toxicity. Formulation development represents an important approach to these problems. Among the many delivery systems studied, polymeric micelles are an attractive nano-scaled delivery system due to their simplicity, ability to solubilize water-insoluble drugs, and small size (10-100 nm) that can take advantage of enhanced permeability and retention effect to specifically accumulate in tumors. This book chapter provides a brief review of recent advancements in developing environmentally responsive micellar systems for controlled delivery of chemotherapeutic agents to tumor tissues. The emphasis is placed on the discussion of several dual functional nanomicellar systems that were recently developed in our laboratory as well as a new strategy of improving micellar formulations via incorporation of an interfacial drug-interactive motif(s).
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Cancer is a major cause of death around the world, especially in USA. The most common cancer treatments are surgery, radiation and chemotherapy, with chemotherapy being the major treatment modality. However, the chemotherapeutic agents are limited by their unsuitable properties, such as low water solubility, toxicity and drug resistance (Mishra et al., 2010; Alexis, et al., 2008; Shapria, et al., 2011). Currently, nanotechnology has been extensively studied for their potential applications in cancer diagnosis and treatment. Various nanocarriers have been developed including liposomes, micelles, dendrimers and nanocrystals.
Most of the nanoparticles use enhanced permeability and retention (EPR) effect which is a property by which molecules of certain sizes (typically liposomes, micelles and macromolecular drugs) tend to accumulate in tumor tissue much more than they do in normal tissues (Matsumura, & Maeda 1986; Duncan, & Sat 1998). In addition, a tumor-specific ligand can be introduced onto the surface of nanoparticles to further facilitate their interaction with tumor cells following accumulation at tumor sites (Michalet, et al., 2005; van Vlerken, et al., 2007). The development of tumor-targeting nano delivery systems has revived the therapeutic uses of many potent chemotherapeutics that are too toxic to be applied in human body directly. In the past decade, polymeric micelles have been utilized as a novel promising colloidal carrier for the targeted delivery and controlled release of drugs, proteins and genes in the cancer diagnosis and therapy. Micelles have a size of 10-200 nm, a structure with the hydrophobic core for efficient loading of poorly water soluble drugs and a layer of hydrophilic shells to warrant excellent colloidal stability and more importantly intrinsic stealth effect (Davis, et al., 2008).
One major advantage of polymeric micellar systems is their simplicity. However, conventional micellar systems suffer from limited drug loading capacity and colloidal stability in the blood circulation. Accordingly, significant efforts have been devoted to resolve these problems. In addition, significant progress has been made in developing intelligent micellar systems that are stable in blood but become destabilized and release payload drug in response to “tumor-specific” microenvironment. This review summarizes recent progress in targeted delivery of chemotherapeutic agents via polymeric systems.