Polymeric micelles in cancer therapy: State of the art

In recent years, polymeric micelles have been extensively utilized in pre-clinical studies for delivering poorly soluble chemotherapeutic agents in cancer. Polymeric micelles are formed via self-assembly of amphiphilic polymers in facile manners. The wide availability of hydrophobic and, to some extent, hydrophilic polymeric blocks allow researchers to explore various polymeric combinations for optimum loading, stability, systemic circulation, and delivery to the target cancer tissues. Moreover, polymeric micelles could easily be tailor-made by increasing and decreasing the number of monomers in each polymeric chain. Some of the widely accepted hydrophobic polymers are poly(lactide) (PLA), poly(caprolactone) (PCL), poly(lactide- co -glycolide) (PLGA), polyesters, poly(amino acids), lipids. The hydrophilic polymers used to wrap the hydrophobic core are poly(ethylene glycol), poly(oxazolines), chitosan, dextran, and hyaluronic acids. Drugs could be conjugated to polymers at the distal ends to prepare pharmacologically active polymeric systems that impart enhanced solubility and stability of the conjugates and provide an opportunity for combination drug delivery. Their nano-size enables them to accumulate to the tumor microenvironment via the Enhanced Permeability and Retention (EPR) effect. Moreover, the stimuli-sensitive breakdown provides the micelles an effective means to deliver the therapeutic cargo effectively. The tumor micro-environmental stimuli are pH, hypoxia, and upregulated enzymes. Externally applied stimuli to destroy micellar disassembly to release the payload include light, ultrasound, and temperature. This article delineates the current trend in developing polymeric micelles combining various block polymeric scaffolds. The development of stimuli-sensitive micelles to achieve enhanced therapeutic activity are also discussed. • Polymeric micelles are self-assembled nano-aggregates of amphiphilic b- co -polymers. • Micelles load drugs physico-chemically, tumor-targeted by active/passive phenomena. • The review focusses on various lipophilic and hydrophilic micellar building blocks. • Micelles sensitive to stimuli, pH, hypoxia, temperature, and light are discussed.