Curcumin-laden hydrogel coating medical device for periprosthetic joint infection prevention and control

Abstract

The Periprosthetic Joint Infection (PJI) is one of the most important complications of the joint arthroplasty. This surgical procedure is rising worldwide and is further affecting the public health because of the widespread resistance to antibiotics. New therapeutic strategies and innovative antimicrobial biomaterials development are needed to eradicate pathogens without inducing resistance and accelerating recovery. In this direction, herein Curcumin I- (Cur-) loaded DAC® (Defensive Antibacterial Coating, a hydrogel based on hyaluronic acid conjugated to polylactic acid, hereafter named DAC) has been built on. To incorporate Cur in the DAC, thus obtaining Cur-DAC (Cur ≅ 0.93 mg/g), the generally recognized as safe (GRAS) propylene glycol (PG) was used as cosolvent. The drugs combinations of Cur (≅ 0.93 mg/g) and Vancomycin (Van) (at low dose that is ≅ 0.033 mg/g) within the hydrogel (Cur/Van-DAC) was alsoexperienced . Hydrogels were prepared and characterized by rheological investigations and their erosion together with the drug release profile over the time evaluated in physiological conditions. The nanohydrogels produced upon water dilution were characterized by AFM, DLS, and UV/Vis absorption and emission spectroscopies. Superior Cur stability over pH-, solvent- and photoinduced degradations resulted in the DAC matrix. The photoinduced antimicrobial activity of Cur-DAC against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium was evaluated by spreading loaded DAC-based hydrogel onto titanium disk mimicking prosthesis, thus detecting a good reduction of bacterial load after 30 min of exposure to light and a subsequent decrease of cells number at 24 h in the absence of nutrients. The drug association in Cur/Van-DAC demonstrated the best activity against MRSA, even in the presence of nutrients, with respect to established DAC loaded with high amounts of Van (ranging from 18.7 mg/g to 45.8 mg/g) used during the surgery, due to the photoantibacterial activity of Cur, becoming promising to prevent and control joint infections.