Abstract
Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is a deadly infection, and increasing resistance worsens an already bad scenario. In this work, a new nanomedicine antibacterial agent, based on dihydroartemisinin (DHA) and chitosan (CS), has been successfully developed to overcome MTB’s drug-resistant. To enhance DHA’s solubility, we have prepared nanoparticles of DHA loaded CS by an ionic crosslinking method with sodium tripolyphosphate (STPP) as the crosslinking agent. The DHA-CS nanoparticles (DHA-CS NPs) have been fully characterized by scanning electron microscopy, Fourier transforms infrared spectroscopy, dynamic light scattering, and ultraviolet spectrophotometry. DHA-CS NPs show an excellent antibacterial effect on the rifampicin (RFP)-resistant strain (ATCC 35838) and, at a concentration of 8.0 μg/ml, the antibacterial impact reaches up to 61.0 ± 2.13% (n = 3). The results of Gram staining, acid-fast staining, auramine “O” staining and electron microscopy show that the cell wall of RFP-resistant strains is destroyed by DHA-CS NPs (n = 3), and it is further verified by gas chromatography-mass spectrometry. Since all the metabolites identified in DHA-CS NPs treated RFP-resistant strains indicate an increase in fatty acid synthesis and cell wall repair, it can be concluded that DHA-CS NPs act by disrupting the cell wall. In addition, the resistance of 12 strains is effectively reduced by 8.0 μg/ml DHA-CS NPs combined with RFP, with an effective rate of 66.0%. The obtained results indicate that DHA-CS NPs combined with RFP may have potential use for TB treatment.
Highlights
Caused by Mycobacterium tuberculosis (MTB), tuberculosis (TB) is a chronic infectious disease with high mortality rate
scanning electron microscope (SEM) results showed that the DHA-CS NPs formed a uniform quasi-spherical shape with low polydispersity, and the diameter was consistent with the above particle size measurement results (Figure 1)
Solid drug sensitivity testing was used to detect whether the combination of DHA-CS NPs and RFP could reduce the resistance of clinical RFP-resistant strains
Summary
Caused by Mycobacterium tuberculosis (MTB), tuberculosis (TB) is a chronic infectious disease with high mortality rate. According to the worldwide progress report on tuberculosis elimination 2020, TB still accounts for the highest mortality from. DHA-CS DPs Inhibit RFP-Resistant MTB any infectious diseases worldwide, causing 1.5 million deaths in 2018. According to the global tuberculosis report 2019, the latest treatment data has shown that the treatment success rate of MDRTB is 56.0%, and extensively severe drug-resistant TB (XDR-TB) is almost impossible to incurable. Both MDR-TB and XDR-TB are resistant to RFP. Developing anti-TB new drugs is a practical approach to the treatment of RFP-resistant TB (Dheda et al, 2014; Maitre et al, 2017)
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