Breaking Hydrogen Bonds Through ROS: Ability of Bioactive Compounds for Improving the Therapeutic Efficacy of Drug‐Delivering Systems
Debraj Chakraborty, Atanu Banerjee, Vivek Chavda, Akanksha Kamble, Arprita Malhan, Ushasi Das, Deepanjan Datta, Subheet Kumar Jain, Ruma Sarkar, Sudarshan SinghABSTRACT
Reactive oxygen species (ROS) are critical mediators in pathological conditions, driving development of ROS‐responsive drug delivery systems for enhanced therapeutic outcomes. The structural stability and functionality of biomaterials‐including hydrogels, gelatin, and chitosan—are governed by hydrogen bonding (HB), a fundamental non‐covalent interaction. However, excessive HB can impair therapeutic efficacy by retarding drug release. This review highlights ROS, elevated in pathological states such as inflammation and cancer, as functional triggers for dynamic control over delivery. Under high‐ROS conditions, bioactive compounds like polyphenols and alkaloids exhibit “redox ambivalence,” switching to pro‐oxidant activity and generating ROS in situ. By exploiting ROS's unique chemical reactivity, these compounds can be engineered to disrupt HB networks, inducing structural transformations in drug carriers. Such changes enable spatiotemporally controlled release of incorporated therapeutics, enhancing site‐specific delivery and efficacy. Moreover, integrating ROS‐responsive bioactive compounds improves drug release kinetics while providing synergistic effects, including ROS scavenging and immune modulation. Consequently, this review examines ROS‐mediated disruption of HB within polymeric carriers and bioactive compounds, facilitating controlled therapeutic release at disease sites.