Work

Hypoxia-responsive hybrid nanoparticles loaded with fingolimod and colistin against multidrug-resistant Klebsiella pneumoniae with mature biofilm

Year: 2025

Type: article

Abstract: Multidrug-resistant Klebsiella pneumoniae (MDR- KP ) is characterized by high mortality and risk of nosocomial transmission, and biofilm constitutes the primary challenge in the treatment of its implant-associated and refractory pulmonary infections. Notably, the hypoxic microenvironment and the physical barrier of biofilm leading to the increased tolerance of the bacteria to antibiotics. Herein, a hypoxia-responsive hybrid nanoparticle (CHLip@FLD/COL) loaded separately with anti-biofilm candidate fingolimod (FLD) and antibiotic colistin (COL) is achieved targeting antibacterial efficacy against MDR- KP in vitro and in vivo . CHLip@FLD/COL is composed of hybridizing hypoxia-responsive lipids (HLipid) and lipid A targeting materials DSPE-mPEG-COL. HLipid is synthesized by hexadecanedioic acid esterified with nitroimidazole, while DSPE-mPEG is coupling with vector COL via amide reaction. The relative level of extracellular polymeric substances and the NIR-IIb sO 2 images of the infection site are used as indicators to establish mature biofilm models. CHLip@FLD/COL readily releases FLD and COL in hypoxic conditions, and its MIC against MDR- KP is only one-sixteenth of that when COL is used alone in vitro . The nanoparticle exhibits bacterial targeting ability and antibacterial effect in the pulmonary infection and biofilm infection mice models. Bacterial loads eliminated by 4 Log 10 CFU and 2 Log 10 CFU, respectively. The strategy provides a valuable reference for the treatment of refractory infections caused by MDR- KP .

Source: Asian Journal of Pharmaceutical Sciences

DOI: 10.1016/j.ajps.2025.101107

Authors: Mengting Liu, Xinrui Liu, Tengli Zhang, Yuanqiang Wang, Hong Yao, Xiwang Liu, Zhiguo Fang, Yinglan Yu, Lei Luo

Institutions: Southwest University, Chinese Academy of Agricultural Sciences, Chongqing University of Technology, Henan Agricultural University

Language: English

Topic: Nanoparticle-Based Drug Delivery

Subfield: Biomaterials

Field: Materials Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: diamond