Drug Delivery-Enabled Antibiofilm Therapeutics from Traditional Chinese Medicine-Derived Bioactives: Recent Advances and Future Perspectives

Biofilm-associated infections remain difficult to treat because the extracellular polymeric substance matrix, charge-selective transport, microenvironmental gradients, and persister formation together limit effective drug exposure and reduce the antimicrobial efficacy. Traditional Chinese Medicine-derived bioactives provide structurally diverse small-molecule payloads with promising antibiofilm potential, but their therapeutic utility is often constrained by poor aqueous solubility, chemical instability, rapid clearance, and insufficient local retention at the infected sites. This Review surveys recent advances in drug delivery-enabled antibiofilm therapeutics based on TCM-derived bioactives, with emphasis on how delivery design addresses distinct biofilm-associated barriers. Representative payload liabilities are first discussed to clarify why formulation design is central to improving performance. Major delivery platforms, including nanoparticles, hydrogels, and microneedle-assisted systems, are then compared by using shared pharmaceutics criteria such as loading strategy, release behavior, penetration, retention, and model relevance. In addition, photodynamic, photothermal, and sonodynamic approaches are examined as combination strategies that can augment delivery-enabled biofilm control. Rather than cataloging natural products or delivery systems, this Review focuses on the relationship among biofilm barriers, payload properties, delivery design, and preclinical evaluation. Current challenges related to model relevance, quality consistency, safety, manufacturability, and further development are also discussed. Overall, this Review aims to provide a practical framework for the rational design of antibiofilm therapeutics based on TCM-derived bioactives.