Temperature- and pH-sensitive Polymeric Micelles for Drug Encapsulation, Release and Targeting
More than 50% of the drugs in the market and 70% of the new candidates are poorly water soluble according to the Biopharmaceutic Classification System (BCS(. Poor aqueous solubility and physico-chemical stability of drugs in biological fluids remain key limitations in oral, parenteral and transdermal administration and contribute to an increase the drug attrition rate. Motivated by the outbreak of nanotechnology, different nanocarriers made of lipids and polymers have been designed and developed to address these limitations. Moreover, robust platforms were exploited to achieve the temporal and spatial release of drugs, thus constraining the systemic exposure to toxic agents and the appearance of severe adverse effects and improving the safety ratio. Owing to unique features such as (i( great chemical flexibility, (ii( capacity to host, solubilize and physico-chemically stabilize poorly water soluble drugs, (iii( ability to accumulate selectively in highly vascularized solid tumors and (iv( ability of single amphiphile molecules (unimers( to inhibit the activity of different pumps of the ATP-binding cassette superfamily (ABCs(, polymeric micelles have emerged as one of the most versatile nanotechnologies. Despite their diverse applications to improve the therapeutic outcomes, polymeric micelles remain clinically uncapitalized. The present chapter overviews the most recent applications of temperature- and pH-responsive polymeric micelles for the encapsulation, release and targeting of drugs and discusses the perspectives for these unique nanocarriers in the near future.