ABSTRACT
Recent advances in synthetic methods of polymerization such as controlled-radical polymerization, encompassing atom transfer radical polymerization, reversible addition-fragmentation chain transfer, and nitroxide-mediated polymerization have allowed more control over polymerization reactions and as such, allowed the development of increasingly sophisticated polymers (Sauer et al., 2001; Checcot et al., 2003; Rakhmatullina et al., 2007). These and other advancements in synthetic techniques have facilitated the development of stimuli-responsive or “smart” drug delivery systems. Stimuli-responsive delivery systems respond to some form of stimuli, be it external or internal. External stimuli are those that are applied from outside the body and include light, magnetic elds, and ultrasound; while internal (also known as proximal) stimuli are those found in the microenvironment of a specic part of the body (e.g., diseased tissue) or a specic cellular compartment (e.g., lysosome). Internal stimuli include pH, redox potential, local temperature, and enzyme overexpression. Regardless of the form of stimuli used to activate the system, the overarching principle remains the same; when the material is activated by its stimulus, it undergoes a physical/chemical change (hydrophobic-hydrophilic balance, oxidation state, secondary structure), which results in the release of entrapped therapeutic payloads. This allows for temporal and spatial control of drug release from the system, which in turn increases drug efcacy, decreases side effects, and enhances the therapeutic window.
