Inhaled pH-Responsive polymyxin B-loaded albumin nanoparticles against pneumonia caused by carbapenem resistant Klebsiella pneumoniae

-PEG-SH are linked to the surface of human serum albumin (HSA) via the conjugation reaction. Subsequently, PMB is loaded through electrostatic interactions to yield PEG-pHSA@PMB. The sulfhydryl groups of PEG-pHSA@PMB interact with mucins to help penetrate mucus after inhaled. In an acidic environment, the protonation of the tertiary amino groups within PEG-pHSA@PMB causes the charge alteration, which leads to the release of PMB. It demonstrated excellent mucus permeability, potent bactericidal activity, and superior bacteriostatic effects compared to sole PMB. Inhalation of PEG-pHSA@PMB significantly reduced the bacterial load in the lungs of mice with CRKP pneumonia, alleviating inflammatory response. Moreover, PEG-pHSA@PMB exhibited good cytocompatibility and biosafety. The novel strategy of the inhalation drug delivery system is promising for the treatment of pneumonia caused by drug-resistant bacteria.