Dual-targeting tigecycline nanoparticles for treating intracranial infections caused by multidrug-resistant Acinetobacter baumannii

• Published in: Journal of nanobiotechnology Vol. 22; no. 1; p. 138
• Main Authors: Lan, Xing, Qin, Shugang, Liu, Huan, Guo, Mengran, Zhang, Yupei, Jin, Xinyang, Duan, Xing, Sun, Min, Liu, Zhenjun, Wang, Wenyan, Zheng, Qian, Liao, Xuelian, Chen, Jinpeng, Kang, Yan, Xie, Yongmei, Song, Xiangrong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.03.2024; BioMed Central; BMC
• Subjects: Acinetobacter baumannii; Acinetobacter infections; Acinetobacter Infections - drug therapy; Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics; Bacterial infections; Biotechnology; Blood-brain barrier; Brain; Central nervous system diseases; Cerebrospinal fluid; Chemical properties; Core-shell particles; Drug delivery systems; Drug resistance in microorganisms; Drug Resistance, Multiple, Bacterial; Drug therapy; Drugs; Efficiency; Ethylenediaminetetraacetic acid; Health aspects; Humans; Infection; Infections; Intracranial infection; Medical research; Medicine, Experimental; Membrane permeability; Microbial Sensitivity Tests; Minocycline - pharmacology; Molecular weight; Multidrug resistance; Multidrug-resistant Acinetobacter baumannii; Nanoparticles; Particle size; Pathogens; Peptides; Permeability; Pharmaceutical research; Pharmacology; Polylactide-co-glycolide; Polyvinyl alcohol; Proteins; Solvents; Surface active agents; Tetracycline; Tetracyclines; Tigecycline; Tigecycline - pharmacology; Tigecycline - therapeutic use; Vehicles; Water; Water chemistry; China; Nanoparticles; Intracranial infection; Multidrug-resistant Acinetobacter baumannii; Tigecycline; Blood–brain barrier
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-024-02373-z

Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood-brain barrier (BBB). In this study, we prepared a novel core-shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aβ11 and Tween 80 (Aβ11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aβ11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation.