Liposomal antibiotic delivery system towards gram-negative bacteria

• Κύριος συγγραφέας: Tezcan, Gozde
• Άλλοι συγγραφείς: Κλεπετσάνης, Παύλος
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2020
• Θέματα: Multidrug resistance; Gram-negative bacteria; Liposomes; Antibiotics; Ανθεκτικότητα μολύνσεων; Gram-αρνητικά βακτήρια; Λιποσώματα; Αντιβιοτικά

The rise of multidrug resistance in Gram-negative bacteria infections is a major public health issue. The main mechanism of resistance in pathogens is emerging from low permeability of Gram-negative bacteria outer membrane to most of the antibacterial agents that are currently available. The aim of this study was assessing the potential of liposomal formulation strategies to repurpose current antibiotics or design new combination therapy with antibacterial agents. This study describes a novel way to enhance antibacterial activity by selective targeting of E.coli and combination therapy with another antibiotic, tetracycline. Fluorescently labelled liposomes were prepared by thin film hydration method and antibacterial activity of liposomes were evaluated by optical density measurement and time-kill assay. The average particle size of colistin encapsulated liposomes were 149.2 ± 16.45 nm with 0.128 PDI demonstrating narrow size distribution. Our results demonstrated that colistin encapsulated liposomes enhance antibacterial activity compared to free colistin via concentration effect which is elucidated as maintaining high local drug concentration at the outer membrane of E.coli leading to outer membrane disruption and subsequently killing of the bacteria. Co-administration of tetracycline and colistin in liposomes showed that antibacterial activity of tetracycline is restored when in combination with colistin in lower concentration. Hence antimicrobial resistance of tetracycline can be mitigated with this approach by exploiting colistin targeting effect. This study establishes a novel pathway to deliver antibiotics specifically by increasing their therapeutic efficiency, minimising systemic exposure and enhancing retention at the site of infection which represents a promising approach for developing delivery strategies for gastrointestinal infections.