2. Academic Validation
  3. Inhaled pH-Responsive polymyxin B-loaded albumin nanoparticles against pneumonia caused by carbapenem resistant Klebsiella pneumoniae

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

  • Mater Today Bio. 2025 Feb 18:31:101590. doi: 10.1016/j.mtbio.2025.101590.
Ziling Li 1 2,  Huiling Lei 3,  Jiannan Hu 1 2,  Tong Zhou 3,  Shuaiqi Yuan 3,  Xinyue Ma 1 2,  Yunfei Zhu 1 2,  Chao Liu 1 2,  Decai Wang 1 2,  Yuzhou Wu 3,  Shuyun Xu 1 2
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
  • 2 Key Laboratory of Respiratory Diseases of National Health Commission, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, 430030, Hubei Province, China.
  • 3 Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, Hubei Province, China.
PMID: 40104651 DOI: 10.1016/j.mtbio.2025.101590
Abstract

The pneumonia induced by carbapenem resistant Klebsiella pneumoniae (CRKP) has high morbidity and mortality. Among the Antibiotics currently available, polymyxin B (PMB) is considered to be the last line of defense. Routine intravenous administration of PMB has many problems, such as severe neurotoxicity and nephrotoxicity. In this study, a novel inhaled PMB-loaded albumin nanoparticles (PEG-pHSA@PMB) capable of penetrating airway mucus and responding to the Infection microenvironment is constructed. An acid-responsive functional molecule (PEBA) and NH2-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.

Keywords

Carbapenem resistance; Klebsiella pneumoniae; Nanoparticles; Pneumonia; Pulmonary delivery.

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