Smart delivery systems for microbial biofilm therapy: Dissecting design, drug release and toxicological features

Bacterial biofilms are highly protected surface attached communities of bacteria that typically cause chronic infections. To address their recalcitrance to antibiotics and minimise side effects of current therapies, smart drug carriers are being explored as promising platforms for antimicrobials. Herein, we briefly summarize recent efforts and considerations that have been applied in the design of these smart carriers. We guide readers on a journey on how they can leverage the inherent biofilm microenvironment, external stimuli, or combine both types of stimuli in a predictable manner. The specific carrier features that are responsible for their 'on-demand' properties are detailed and their impact on antibiofilm property are further discussed. Moreover, an analysis on the impact of such features on drug release profiles is provided. Since nanotechnology represents a significant slice of the drug delivery pie, some insights on the potential toxicity are also depicted. We hope that this review inspires researchers to use their knowledge and creativity to design responsive systems that can eradicate biofilm infections.