Nanotechnology Strategies to Mitigate Antimicrobial Resistance in Fish Aquaculture Systems

Abstract Aquaculture plays an increasingly important role in global food production, but intensive freshwater fish aquaculture still faces major challenges related to infectious diseases and the use of antimicrobials. Antimicrobials are commonly administered orally through medicated feed, a practice often compromised by drug leaching before ingestion, heterogeneous feed intake, and temperature- and species-dependent pharmacokinetic variability. These factors can generate heterogeneous antimicrobial exposure in fish, ranging from subtherapeutic concentrations to compensatory overdosing practices while simultaneously increasing the entry and persistence of antimicrobial residues in water and sediments, thereby creating selective pressure that favors the emergence and maintenance of antimicrobial resistance (AMR) in aquatic microbial communities. This integrative review focuses primarily on intensive freshwater fish aquaculture systems and examines how antimicrobial use contributes to AMR through interconnected pharmacological, microbiological, and environmental pathways. The review discusses how water temperature, fish physiology, feeding behavior, and dosing inconsistencies influence antimicrobial absorption, disposition, therapeutic performance, residue persistence, and resistance selection. Intrinsic, acquired, and adaptive resistance mechanisms are also discussed with emphasis on the role of environmental contamination in maintaining resistance reservoirs. Within this framework, the review analyzes nanoenabled strategies designed to address these bottlenecks, including drug delivery systems that improve control over drug administration, gastrointestinal stability, bioavailability, and release, as well as nanotechnologies for residue removal and environmental monitoring. By integrating host- and environment-oriented perspectives, this Review highlights how nanotechnology may help reduce antimicrobial dependence, limit selective pressure, and support more sustainable fish aquaculture within a One Health framework.