Biofunctionalization of Poly(lactide-co-glycolic acid) Using Potent NorA Efflux Pump Inhibitors Immobilized on Nanometric Alpha-Zirconium Phosphate to Reduce Biofilm Formation

Abstract

Polymeric composites, where bioactive species are immobilized on inorganic nanostructured matrix, have received considerable attention as surfaces able to reduce bacterial adherence, colonization, and biofilm formation in implanted medical devices. In this work, potent in-house S. aureus NorA efflux pump inhibitors (EPIs), belonging to the 2-phenylquinoline class, were immobilized on nanometric alpha-zirconium phosphate (ZrP) taking into advantage of acid-base or intercalation reactions. The ZrP/EPI were used as filler of poly(lactide-co-glycolic acid) (PLGA) to obtain film composites with a homogeneous distribution of the ZrP/EPI fillers. As reference, PLGA films loaded with ZrP intercalated with thioridazine (TZ), that is recognized as both a NorA and biofilm inhibitor, and with the antibiotic ciprofloxacin (CPX) were prepared. Composite films were characterized by X-ray diffraction, scanning electron microscopy, and thermogravimetric analysis. The ability of the composite films, containing ZrP/EPI, to inhibit biofilm formation was tested on Staphylococcus aureus ATCC 29213 and Staphylococcus epidermidis ATCC 12228, and it was compared with that of the composite loaded with ZrP/TZ. Finally, the antibacterial activity of CPX intercalated in ZrP was evaluated when used in combination with ZrP/EPI in the PLGA films.

Immobilization of Alendronate on Zirconium Phosphate Nanoplatelets

“…The topotactic exchange method can be considered an alternative to the preparation, via the intercalation reaction, of drug delivery systems based on ZP compounds. In this scenario, the intercalation of drugs such as doxorubicin [ 11 ] and 5-fluorouracil [ 12 ], chlorhexidine [ 13 ], methylene blue as a photosensitizer [ 14 ], and NorA efflux pump inhibitors [ 15 ] was successfully performed on ZP supports. Thus, ZPs have shown promising results as nanocarriers for drug delivery and other biotechnological applications [ 1 ].…”

Overcoming Antibiotic Resistance: Playing the ‘Silver Nanobullet’ Card

“…Now more than ever, the escalating crisis of antibiotic resistance is pressing science to take action in order to stave off a tremendous decline towards a post-antibiotic era [ 3 ]. This quest includes the diffusion of new drugs [ 4 , 5 ], the repurpose of older ones [ 6 ], the administration of mixed antibiotic regimens [ 7 , 8 ], and the testing of target-based approaches focused on the development of specific inhibitors [ 9 , 10 ]. Another strategy involves the combination of antibiotics with metal nanoparticles (NPs).…”