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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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Protein-based polymeric polyelectrolytes are emerging as alternative synthetic nanoparticles owing to their biodegradability and biocompatibility. However, potential in vivo toxicity remains a significant challenge. Herein an array of protein polyelectrolytes generated from cationic human serum albumin (cHSA) and polyethylene glycol (PEG) are synthesized via synthetic customization as antimicrobials for the treatment of systemic infections. By varying PEG molecular weight and chain length, in vitro hemolytic activity can be fine-tuned without significantly affecting antimicrobial potency. The optimal hybrid material, PEG (2000) 18 -cHSA, with potent antimicrobial character, low hemolytic activity, and in vitro biofilm disruptive properties is identified. Surface plasmon resonance (SPR) evaluation demonstrates significantly higher binding activity of the protein nanoparticles to bacteria cell wall components and microfluidic live-cell imaging indicates that the nanoparticles act through a membranolytic mechanism. Given their low susceptibility to drug resistance and potent activity against resistant bacteria strains, these findings establish the PEGylated albumin nanoparticles as a potent weaponry against drug resistance and biofilm-related infection., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

While physically crosslinked polycarbonate hydrogels are effective drug delivery platforms, their hydrophobic nature and lack of side chain functionality or affinity ligands for controlled release of hydrophilic drugs underscore the importance of their chemical compositions. This study evaluates an array of anionic hydrogel systems of phenylboronic acid functionalized triblock copolymers prepared via reversible physical interactions. Variation of key chemical functionalities while maintaining similar core structural features demonstrates the influence of the substitution position and protection of the boronic acid functionality on gel viscoelasticity and mechanical strength at physiological pH. The optimum gel systems obtained from the meta-substituted copolymers (m-PAP) are stable at physiological pH and nontoxic to mammalian dermal cells. The polymyxin B loaded m-PAP hydrogels demonstrate controlled in vitro drug release kinetics and in vitro antimicrobial activity against Pseudomonas aeruginosa over 48 h. In vivo antimicrobial efficacy of the drug loaded hydrogels further corroborates the in vitro results, demonstrating sustained antimicrobial activity against P. aeruginosa burn wound infections. The current strategy described in this study demonstrates a straightforward approach in designing physiologically relevant boronic acid hydrogel systems for controlled release of cationic antimicrobials for future clinical applications., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)