Outlook on the Application of Metal-Liganded Bioactives for Stimuli-Responsive Release

Direct metal-liganded bioactive coordination complexes are known to be sensitive to stimuli such as pH, light, ion activation, or redox cues. This results in the controlled release of the bioactive(s). Compared to other drug delivery strategies based on metal complexation, this type of coordination negates a multi-step drug loading methodology and offers customized physiochemical properties through judicious choice of modulating ancillary ligands. Bioactive release depends on simple dissociative kinetics. Nonetheless, there are challenges encountered when translating the pure coordination chemistry into the biological and physiological landscape. The stability of the metal–bioactive complex in the biological milieu may be compromised, disrupting the stimuli-responsive release mechanism, with premature release of the bioactive. Research has therefore progressed to the incorporation of metal-liganded bioactives with established drug delivery strategies to overcome these limitations. This review will highlight and critically assess current research interventions in order to predict the direction that pharmaceutical scientists could pursue to arrive at tailored and effective metal-liganded bioactive carriers for stimuli-responsive drug release.