Thermosensitive polymeric micelles for targeted drug delivery

Thermosensitive polymers are characterized by temperature-dependent aqueous solution properties. Below their lower critical solution temperature they are in an expanded state and fully dissolved, while above it they are dehydrated and insoluble. This has been exploited for the development of polymeric micelles that can be formed or destabilized depending on the solution temperature. Many micelle forming thermosensitive polymers have been described in literature, among which poly(N-isopropylacrylamide) (pNIPAAm), Pluronics (triblock copolymers of polypropylene oxide middle block flanked by two polyethylene oxide blocks) and poly(hydroxypropyl methacrylamide-lactate) (p(HPMAm-Lac(n))) are the most frequently studied and some drug-loaded formulations based on thermosensitive polymers have reached clinical trials. The first generation of micelles composed of thermosensitive polymers was based on mere hydrophobic interactions between polymer blocks, while more recently shell or core crosslinking was introduced, in order to improve their stability in the circulation after intravenous administration and therefore, the accumulation of their depot in diseased areas. Various formulations of drug-loaded micelles based on thermosensitive polymers have shown promising results in vitro, as well as in vivo. This review gives an overview of the most important recent developments regarding the design and synthesis of various types of thermosensitve polymers for drug delivery.