Antimicrobial activity against Staphylococcus aureus and respiratory biocompatibility of inhaled rifampicin nanoparticles

DE LA CRUZ-THEA B.; SCOLARI I.R.; MUSRI M.M.; PÁEZ P.L.; GRANERO G.E.

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia 2019, SAlC, SAFE, SAB, SAP, AACYTAL, NANOMED-AR, HCS; 2019

Infections caused by intracellular bacteria in the lower respiratory tract are among the most important causes of death worldwide. In particular, pulmonary intracellular infections are difficult to eradicate due to various contributing factors 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, this work aimed to evaluate polymeric nanoparticles (NPs) as efficient carriers of rifampicin (RIF) for the treatment of intracellular lung infections. To this end RIF loaded NPs were incubated with human lung-derived cell lines and tested for cytotoxicity, uptake capacity and antimicrobial activity against S. aureus. MTT assay was carried out to study NPs cytotoxicity in human fetal lung fibroblast cells (MRC5 cell line) and adenocarcinomic human alveolar basal epithelial cells (A549 cell line). The cellular uptake capacity of RIF NPs was studied by confocal laser scanning microscopy (CLSM) and the drug quantification by high performance liquid chromatography (HPLC). Finally, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in different S. aureus strains were determined and interactions between NPs and bacterial cells were evaluated by CLSM.RIF NPs had less cytotoxicity than free RIF and were internalized by lung cells. Moreover, RIF NPs showed a significant improvement in antimicrobial activity against S. aureus strains. The interfacial assembly of NPs in the bacterial membrane was determined by CLSM, which indicated a strong interaction between bacteria and NPs, this was a key contributors to the biocide activity of proposed nanocarrier.The findings of this work show that RIF polymeric NPs could be an adequate system for the delivery of antibiotics which are known to be losing efficacy due to acquired antimicrobial resistance, with promising prospects regarding effective treatment of pulmonary intracellular infections.