pH-Sensitive Polymer–Drug Conjugates

Polymer–drug conjugates (PDCs) were introduced with the goal of improving the properties of drug molecules, such as their solubility, blood circulation time, and tissue targeting. Since the first examples dating back decades, substantial progress has been made in the design and implementation of linkages that enable the selective release of drugs in response to physiological stimuli associated with various pathologies. Among these stimuli, a change in pH from neutral to mildly acidic has been one of the most widely exploited. This perspective will discuss the advantages and limitations of different linker strategies and their applications in the development of PDCs to treat cancer, inflammation, and bacterial infection. These materials range from soluble linear and branched polymer systems to nanoparticles, hydrogels, and coatings. Both an historical perspective and recent developments will be presented. Finally, some ongoing challenges will be discussed, along with opportunities for future work.