Rifampicin loaded in alginate/chitosan nanoparticles as a promising pulmonary carrier against Staphylococcus aureus
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ORIGINAL ARTICLE
Rifampicin loaded in alginate/chitosan nanoparticles as a promising pulmonary carrier against Staphylococcus aureus I. R. Scolari 1 & P. L. Páez 1 & M. M. Musri 2,3 & J. P. Petiti 4 & A. Torres 4 & G. E. Granero 1
# Controlled Release Society 2019
Abstract This study aims to explore the antimicrobial activity of rifampicin (RIF) and ascorbic acid (ASC) co-loaded into alginate (ALG)/ chitosan (CS) nanoparticles (RIF/ASC NPs) and tested for their antibacterial activity against several strains of methicillinsensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). Also, the present research focused on exploring the possible antibacterial mechanism of action of these RIF/ASC NPs, which demonstrated a significant biocide activity against the S. aureus strains with minimum inhibitory concentrations (MIC) between 2- and 8-fold lower than those one exhibited with the free antibiotic RIF. The proposed antimicrobial mechanism of action of the RIF/ASC NPs seems to be the result of collaborative effects between NPs and the RIF/ASC antibiotic combination. Moreover, results indicated that the functionalized RIF/ASC NP surface played a crucial role on the processes of NP adhesion into the bacterial surface, the alterations on the cell membrane integrity, and the cell uptake of the RIF/ASC antibiotic into bacteria. Further, the in vivo lung deposition pattern of empty NPs labeled (NPs-FITC) with isothiocyanate fluorescein in rats was investigated post intratracheal instillation of NPs. In summary, findings from this work show that our novel designed engineered RIF/ASC co-loaded NPs could be a suitable system for antibiotic lung administration with promising perspectives for effective treatments of pulmonary intracellular infections for those known antibiotics that are losing effectiveness due to antimicrobial resistance problems. Keywords Antibacterial mechanism . Polymeric glyconanoparticles . Pulmonary delivery . Rifampicin
Introduction Bacterial infections are among the biggest global health problems not only due to they are associated with morbidity and mortality but also because of the frequent appearance of
* G. E. Granero [email protected] 1
Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA - CONICET) and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, X5000HUA Córdoba, Argentina
2
Instituto de Investigación Médica Mercedes y Martín Ferreyra, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Córdoba (INIMEC-CONICET-UNC), Córdoba, Argentina
3
Facultad de Ciencias Exactas Físicas y Naturales, Universidad Nacional de Córdoba, Córdoba, Argentina
4
INICSA, CONICET Centro de Microscopía Electrónica, Universidad Nacional de Córdoba, X5000HUA Córdoba, Argentina
bacterial resistant to treatments, which leads to an urgent need to develop new strategies that efficiently fight infections [1]. Staphylococcus aureus, the causative agent of a wide variety of
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