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Drug-resistant infectious diseases pose a substantial challenge and threat to medical regimens. While adaptive laboratory evolution provides foresight for encountering such situations, it has inherent limitations. Novel drug delivery systems (DDSs) have garnered attention for overcoming these hurdles. Multi-stimuli responsive DDSs are particularly effective due to their reduced background leakage and targeted drug delivery to specific host sites for pathogen elimination. Bacterial infections create an acidic state in the microenvironment (pH: 5.0–5.5), which differs from normal physiological conditions (pH: 7.4). Infected areas are characterized by the overexpression of hyaluronidase, gelatinase, phospholipase, and other virulence factors. Consequently, several effective stimuli-responsive DDSs have been developed to target bacterial pathogens. Additionally, biofilms, structured communities of bacteria encased in a self-produced polymeric matrix, pose a significant challenge by conferring resistance to conventional antimicrobial treatments. Recent advancements in nano-drug delivery systems (nDDSs) show promise in enhancing antimicrobial efficacy by improving drug absorption and targeting within the biofilm matrix. nDDSs can deliver antimicrobials directly to the biofilm, facilitating more effective eradication of these resilient bacterial communities. Herein, this review examines challenges in DDS development, focusing on enhancing antibacterial activity and eradicating biofilms without adverse effects. Furthermore, advances in immune system modulation and photothermal therapy are discussed as future directions for the treatment of bacterial diseases. [ABSTRACT FROM AUTHOR]

Tetrahedral amorphous carbon (taC) is a hydrogen-free carbon with extensive properties such as hardness, optical transparency, and chemical inertness. taC coatings have attracted much attention in recent times, as have coatings doped with a noble metal. A known antimicrobial metal agent, silver (Ag), has been used as a dopant in taC, with different Ag concentrations on the Ti64 coupons using a hybrid filtered cathodic vacuum arc (FCVA) and magnetron sputtering system. The physiochemical properties of the coated surface were investigated using spectroscopic and electron microscopy techniques. A doping effect of Ag-taC on biofilm formation was investigated and found to have a significant effect on the bacterial-biofilm-forming bacteria Staphylococcus aureus and Pseudomonas aeruginosa depending on the concentration of Ag. Further, the effect of coated and uncoated Ag-taC films on a pathogenic bacterium was examined using SEM. The result revealed that the Ag-taC coatings inhibited the biofilm formation of S. aureus. Therefore, this study demonstrated the possible use of Ag-taC coatings against biofilm-related complications on medical devices and infections from pathogenic bacteria. [ABSTRACT FROM AUTHOR]