In vitro study of nanoliposomes containing curcumin and doxycycline for enhanced antimicrobial photodynamic therapy against Aggregatibacter actinomycetemcomitans

The excessive inappropriate use of systemic antibiotics has contributed to the emergence of antibiotic-resistant pathogens, which pose a significant risk to the success of treatment. This study has approached this problem by developing doxycycline-loaded liposome doped with curcumin (NL-Cur(+Dox)) for combination antibacterial therapy against Aggregatibacter actinomycetemcomitans. The characterization of formulation revealed encapsulation of both drugs in NL-Cur(+Dox) with an average size of 239 nm and sustained release behavior. Transmission electron microscopy analysis confirmed the vesicular-shaped nanocarriers without any aggregation or crystallization. The cytotoxic and hemolytic activities of NL-Cur(+Dox) were evaluated. The anti-biofilm and anti-metabolic effects of NL-Cur(+Dox) -mediated antimicrobial photodynamic therapy (aPDT) were examined. The data indicated that NL-Cur(+Dox) -mediated aPDT led to a significant reduction of biofilm (82.7%, p = 0.003) and metabolic activity (75%, p < 0.001) of A. actinomycetemcomitans compared to the control. NL-Cur(+Dox) had no significant cytotoxicity to human gingival fibroblast cells under selected conditions (p = 0.074). In addition, the hemolytic activity of NL-Cur(+Dox) were negligible (< 5%). These findings demonstrate the potential application of such potent formulations in reducing one of the main bacteria causing periodontitis where the NL-Cur(+Dox) could be exploited to achieve an improved phototherapeutic efficiency.