Encapsulated Phytochemicals for Combating Multidrug-Resistant Bacterial Pathogens and Biofilms: From Delivery Design to Translational Challenges

Antimicrobial resistance (AMR) and biofilm-associated infections represent major therapeutic challenges because they reduce antimicrobial susceptibility, promote persistence, and limit the effectiveness of conventional treatments. Phytochemicals offer a complementary strategy due to their multitarget antimicrobial and antibiofilm activities, including membrane disruption, oxidative stress induction, quorum-sensing interference, efflux-pump inhibition, and disruption of extracellular polymeric substances. However, their clinical application is frequently restricted by poor aqueous solubility, chemical instability, rapid degradation, limited bioavailability, and insufficient accumulation at infection sites. Encapsulation provides a means to overcome these limitations through physicochemical protection, controlled release, and improved local delivery. This review examines the main delivery platforms used to formulate antibacterial phytochemicals against multidrug-resistant and biofilm-associated bacterial pathogens, with emphasis on how carrier materials and formulation parameters influence antimicrobial and antibiofilm activity. Translational applications in antimicrobial coatings, medical devices, wound and burn infections, and combination therapies are critically discussed. Current limitations related to manufacturing scalability, reproducibility, safety, regulatory classification, methodological heterogeneity, and the limited progression from in vitro studies to clinically relevant models are also discussed. Overall, encapsulation can expand the therapeutic potential of phytochemicals, but future progress will depend on demonstrating reproducible advantages over free compounds through standardized formulation, appropriate controls, relevant preclinical models, and early integration of safety and regulatory requirements.