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The existence of biofilms as heterogeneous structures, comprising bacterial cells embedded in a self-synthesized polymeric matrix and adhered to biotic and abiotic surfaces, exhibiting high antibiotic tolerance, is a fact that, in recent years, has exerted selective pressure on healthcare systems with the emergence of numerous infections. This review provides a historical overview of the emergence of biofilms, the latest insights into their functionality and distribution, as well as data on innovative strategies to combat them. Special attention is given to significant diseases caused by biofilms, alongside current data on the molecular mechanisms underpinning their tolerance and resistance. [ABSTRACT FROM AUTHOR]

Biofilms are a well-known multifactorial virulence factor with a pivotal role in chronic bacterial infections. Their pathogenicity is determined by the combination of strain-specific mechanisms of virulence and the biofilm extracellular matrix (ECM) protecting the bacteria from the host immune defense and the action of antibacterials. The successful antibiofilm agents should combine antibacterial activity and good biocompatibility with the capacity to penetrate through the ECM. The objective of the study is the elaboration of biofilm-ECM-destructive drug delivery systems: mixed polymeric micelles (MPMs) based on a cationic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA35-b-PCL70-b-PDMAEMA35) and a non-ionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO100-b-PPO65-b-PEO100) triblock copolymers, loaded with ciprofloxacin or azithromycin. The MPMs were applied on 24 h pre-formed biofilms of Escherichia coli and Pseudomonas aeruginosa (laboratory strains and clinical isolates). The results showed that the MPMs were able to destruct the biofilms, and the viability experiments supported drug delivery. The biofilm response to the MPMs loaded with the two antibiotics revealed two distinct patterns of action. These were registered on the level of both bacterial cell-structural alterations (demonstrated by scanning electron microscopy) and the interaction with host tissues (ex vivo biofilm infection model on skin samples with tests on nitric oxide and interleukin (IL)-17A production). [ABSTRACT FROM AUTHOR]

The self‐organization of microbes into biofilms provides multiple benefits including tolerance to mechanical stress and resistance to immune defences and antibiotics. Coupled to a compromised mucociliary function, these traits have dire consequences in cystic fibrosis patients – persistent infections are the main reason for morbidity and mortality. Thereby, disease progression is associated with universal colonization by Pseudomonas aeruginosa, which selects for a slimy phenotype to adapt to the lung microenvironment. Recognizing this, drug‐delivery vehicles that break down the mucoid extracellular matrix made of alginate are designed to enable better penetration and biofilm dispersion. In parallel, a protective layer responds to the proteolytic activity of the pathogen and thus controls drug availability. To realize this architecture, silica nanoparticles are loaded with imipenem, and then coated with elastin and alginate lyase in a layer‐by‐layer fashion using ultrasound. The nanoscale formulations eradicate up to 80% of the total biomass and reduce the bacterial viability in biofilms by 3 logs, considerably outperforming the bulk antibiotic in vitro, whereby the effects are correlated to changes in the viscoelasticity. Furthermore, the stimuli‐responsive nanocarriers are safe and effective in animal models of P. aeruginosa infection, presenting a considerable therapeutic promise in the challenging context of lung diseases. [ABSTRACT FROM AUTHOR]