Among the innovative strategies found in basic research publications, nanotechnologies cover 12.9% of the selected reviews. Notably, only 0.9% of clinical trials involve nanotechnologies. The difference is even more pronounced if we look at specific types of materials: liposomes are the only type of nanoparticles (NPs) assessed in clinical trials, whereas in basic research literature we found a wide variety of materials, shapes, dimensions, and mechanisms of action (direct activity or drug delivery systems). NPs and nanotools [i,ii], both of biological [iii,iv] and chemical origin, allow several potential advantages compared to traditional strategies. These structures can interact with the biofilm in a three-step process: transport of nanomaterials in its vicinity; attachment to its surface; and migration inside its matrix [v]. They can penetrate the biofilm matrix and deliver molecules with antimicrobial properties, enhancing their permeability and limiting their toxic effect, or they can have antibiofilm effects themselves, such as reactive species generation or closing channels inside the biofilm structure [vi].
Some of these innovative antibiofilm strategies are still far from reaching the clinical practice. Practical limitations arise from the difficulty of manipulation of nanomaterials for large-scale manufacturing, as their properties can be easily altered. Scaling up from the bench to industrial scale is still a challenging task [vii]. Other limitations of chemical and biological NPs are related to high production cost, possible toxic reaction residues, and difficult recovery process [viii]. Despite of their versatility and their promising future biomedical applications [ix,x,xi], NP toxicological profile and host immune response need to be thoroughly investigated and are largely influenced by their solubility, charge and form [i]. Their toxic effects and biocompatibility are still debated in the literature [xii] and research is now focused on finding standard models to test these materials. The factors discussed above explain the very low number of clinical trials involving nanoparticles compared with the basic or pre-clinical applications of these agents [xiii,xiv].
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