Development of an antimicrobial agent with a promissing use in wound healing management

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2019

Infections caused by intracellular bacteria in the lower respiratory tract are one of the most leading causes of death worldwide. In particular, pulmonary intracellular infections are difficult to eradicate due to various contributing factors, among them are the protective niche that bacteria find in the host allowing their survival, protecting them against the guest´s humoral response and the antibiotic therapy, which might lead to the emergence of antibiotic-resistance. Nanotechnology is a very promising technological tool to combat health problems associated with the loss of effectiveness of currently used antibiotics. Based on this problem, the work aims were to evaluate the cytotoxicity and uptake capacity in models of lung cell lines of polymeric NPs developed as transport systems of RIF and determine their antimicrobial activity against strains of S. aureus for treatment of intracellular lung infections.The cytotoxicity of the NPs was studied by the MTT assay in MRC5 and A549 cell lines. In addition, the interaction of NPs with respiratory system components such as mucin and pulmonary surfactant was evaluated by DLS and SEM. On the other hand, the uptake capacity was studied by CLSM and quantification by HPLC. Finally, MIC and MBC in S. aureus strains were determined and the interaction of NPs with bacterial cells was evaluated by CLSM.RIF NPs did not interact with the components of the respiratory system and had a better cytotoxicity than free RIF, they were also internalized by the cell lines studied. On the other hand, they showed a significant improvement in the antimicrobial activity against the S. aureus strains tested and a superficial interaction of the NPs with the bacterial cells was evidenced.The findings of this work showed that RIF polymeric NPs could be an adequate system for the administration of antibiotics with promising prospects for effective treatments of pulmonary intracellular infections for those known antibiotics that are losing efficacy due to antimicrobial resistance problems.