ABSTRACT

Numerous pharmacological active compounds have been discovered, isolated, and synthesized in the last few decades. Many of these promising compounds did not advance beyond the laboratory bench to the clinical setting because of dif culties in nding a suitable delivery system. The colloidal drug delivery system (DDS) provides a crucial approach for problematic drug candidates and gives a solution to the hurdles involved in conventional drug delivery (Boyd, 2008). Colloidal science is often de ned as the science of materials with a length scale below 1 μm, mostly in the sub-100-nm regime. Particle size is often the primary property of concern in a colloidal system and its nal application. The huge surface area that results from dividing a mass of materials down to colloidal dimension offers an important advantage in terms of tailoring the surface properties and subsequent modi cation of particle behavior. In terms of drug delivery, exibility in tailoring the internal structure and surface has led to the adoption of colloidal drug carriers as a platform for a wide range of existing products as a means to achieve new delivery modes for existing drugs and to improve their therapeutic pro le. In order to improve the speci c delivery of drugs with a low therapeutic index, several drug carriers such as liposomes (Krauze et al., 2006), microparticles (Guglielmini, 2008), nanoparticles (Sahoo et al., 2002), drug-polymer conjugates (Sahoo et al., 2007), and polymeric

6.1 Introduction .......................................................................................................................... 157 6.2 Drug Delivery Principle and Challenge ............................................................................... 158 6.3 Composition of Micellar Structure ....................................................................................... 159 6.4 Micellar System as Drug Delivery System ........................................................................... 161 6.5 Functionalization of Polymeric Micelles .............................................................................. 163

6.5.1 Folic Acid as Ligand ................................................................................................. 164 6.5.2 Protein as Ligand ...................................................................................................... 165 6.5.3 Antibody as Ligand .................................................................................................. 166 6.5.4 Aptamer as Ligand.................................................................................................... 166 6.5.5 Other Molecules as Ligands ..................................................................................... 166

6.6 Stealth Polymeric Micelles as Drug Delivery Systems ........................................................ 167 6.7 Micelles as Diagnostic Agent ............................................................................................... 169 6.8 Future Prospects and Conclusion ......................................................................................... 170 Acknowledgment ........................................................................................................................... 171 Abbreviations ................................................................................................................................. 171 References ...................................................................................................................................... 172

micelles (Sutton et al., 2007) have been developed. In recent years, polymeric micelles have been the object of growing scienti c attention for the solubilization and tumor-targeted delivery of chemotherapeutic agents after systemic administration (Rijcken et al., 2007). They are becoming a powerful nanomedicine platform for therapeutic application because of their small size (10-100 nm), good in vivo biocompatibility, stability, and successful use in pharmaceuticals to solubilize waterinsoluble drugs. They are often compared to naturally occurring carriers such as viruses or lipoproteins (Jones and Leroux, 1999; Sutton et al., 2007). The nanoscopic dimension, stealth properties induced by the hydrophilic polymeric brush on the micellar surface, capacity for stabilized encapsulation of hydrophobic drugs offered by the hydrophobic and rigid micellar core, and possibility for the chemical manipulation of the core-shell structure have made polymeric micelles one of the most promising carriers for drug delivering, targeting, and imaging.