Strategies to prepare polymers with cleavable linkages releasing active agents in acidic media

Incorporating labile bonds in the chemical structure of polymers yields interesting materials that are responsive to changes in environmental stimuli, such as pH. Active agents can be conjugated to various polymers through acid-labile linkages, conferring upon them spatiotemporal control over the cleavage and subsequent release of drugs, antibacterial agents or corrosion inhibitors. One key factor influencing the release of active agents is the hydrolytic stability of the linkages. We compared the hydrolytic kinetics of acid-cleavable linkages and discuss the effect of structural fine tuning of molecules on the hydrolysis rate. Synthetic routes towards various acid-sensitive linkages are discussed in relation with the functional unit available on the active substances to be released.