ADMCs-derived exosomal vesicles encapsulated with rifampicin to attenuate Klebsiella pneumonia-induced pediatric lung inflammation: In-vitro and In vivo studies.
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In the current scenario, Klebsiella pneumoniae-induced pediatric lung inflammation is a major health issue, made worse by multidrug-resistant infection. Mainly, Carbapenem-resistant K. pneumoniae (CR-K.pneu) infections are rising due to antimicrobial resistance, highlighting the urgent need for effective treatments. Additionally, lung inflammation can complicate the treatment of lung cancer, as it may hinder therapeutic responses. Herein, the study aimed to explore the adipose mesenchymal stem cells derived exosomal vesicles (ADMSCs-EVs) loaded with rifampcin (Rf) against CR-K. pneu infection in mice model. ADMSCs-EVs were extracted by the ultracentrifugation method and characterized via UV-visible spectra, FTIR, TEM, DLS and Zeta potential. It exhibited strong antioxidant potential confirmed via DPPH assays. The antibacterial assay was significantly inhibited at 100 μg/ml of ADMSCs-EVs-Rf against CR-K.pneu. Light microscopy displays biofilm eradication at the doses of 75 and 100 μg/ml. In vitro biocompatibility of ADMSCs-EVs-Rf enhances proliferation, suppresses oxidative stress, accelerates wound healing, and significantly attenuates inflammatory cytokine production in LPS-induced pediatric NHBE cells. Further, the in vivo antibacterial activity of ADMSCs-EVs-Rf was examined in a CR-K.pneu infection mice model. The treatment significantly decreased MDA levels while increasing the antioxidant markers GSH, SOD, and CAT (p < 0.05), indicating attenuation of oxidative stress. The biocompatibility of ADMSCs-EVs-Rf showed low toxicity at 5 mg/ml. ADMSCs-EVs-Rf may be useful for treating inflammation, fixing damaged cells, clearing out alveolar fluid, and getting rid of microbes. Hence, ADMSCs-EVs-Rf might be a promising option for treating CR-K. pneu infections, particularly those affecting children's respiratory systems and lung cancer.