Strategies for biofilm inhibition: the role of synthetic drug- and nanotechnology-based agents.

Biofilms are organized microbial communities that are surrounded by a matrix of extracellular polymeric substance (EPS), which raises significant challenges to environmental, and medical applications. Their intricate architecture and adaptive behavior enable them to resist conventional antimicrobial therapies, primarily due to restricted drug diffusion, altered metabolic activity, and the emergence of resistance mechanisms. To address these challenges, synthetic drug-based strategies have emerged, focusing on the disruption of key stages in biofilm development, such as bacterial adhesion, quorum sensing (QS), EPS production, and biofilm maturation. Quorum sensing inhibitors, including synthetic furanones, peptide-based inhibitors, and nanoparticles, have shown promising results in interfering with biofilm signaling pathways and preventing biofilm maturation. EPS matrix, such as chelating agents and enzymatic treatments, weaken the biofilm matrix, rendering the microbial cells more susceptible to antimicrobial agents. Nanotechnology-driven approaches, utilizing metal nanoparticles, functionalized nanoparticles, and nanocarrier-based drug delivery systems, enhance. These strategies enhance antimicrobial penetration and efficacy while reducing off-target effects; however, clinical translation is limited by cytotoxicity, pharmacokinetic constraints, and microbial adaptation. Future work should prioritize multi-targeted therapies, personalized biofilm disruption, and advanced drug delivery systems to combat biofilm-related infections and industrial biofouling.