Controlling Release Kinetics of Payloads from Polymer Conjugates by Hydrophobicity

Abstract Polymers conjugated with active molecules are useful for controlled delivery of corrosion inhibitors, phytosanitary products, and drugs. To avoid detrimental side effects, active molecules need to be selectively released upon specific external stimuli. Imine groups are highly acid‐labile linkages that are usually hydrolyzed in a few hours even in neutral medium, which can be detrimental when slow release of payloads is needed. Herein, release kinetics are adjusted by controlling hydrophobicity of pH‐responsive polymers. 5‐(Aminomethyl)‐8‐hydroxyquinoline (AM8HQ), an effective corrosion inhibitor, is conjugated via imine linkage to aldehyde pendant groups in three different copolymers. Release kinetics of AM8HQ from polymer nanoparticles are investigated in acidic and neutral media. Very fast release from polymethacrylate‐based and slow release from polystyrene‐based polymer conjugates clearly show that adjusting the hydrophobicity of the polymer backbone is an effective synthetic strategy to control the cleavage rate of highly labile imine bonds.