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

Abstract

Abstract 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. baumanniiinfections. 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 developed a novel nanocarrier, integrating a dual-targeting peptide Aβ11 and Tween 80 modification (Aβ11/T80@CSs), specifically designed to enhance TGC delivery 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.