Brain inflammatory diseases have become a global concern in clinical care due to the emergence of antibiotic-resistant bacteria, making it increasingly difficult to treat these infections. Broad-spectrum antibiotics face difficulties penetrating the outer bacterial cell wall and the biofilms that bacteria form. Therefore, there is a growing need to develop alternative means for treating bacterial infections such as bacterial meningitis. To address this need, we report the use of pH-sensitive liposomes, which present a more fluid lipid bilayer and promote the destabilization of biological membranes, to deliver targeted antibiotics at the site of infection, notably inside the bacterial cell. The functionalization of the liposomes with cell-penetrating peptides (TAT 47-57) allows them to cross the blood brain barrier (BBB). To this end, we investigated the effect of TAT-functionalized liposomes loaded with antibiotics to inhibit the growth of bacteria commonly associated with bacterial meningitis, including Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli. The results from this study demonstrated excellent growth inhibitory effects of TAT-functionalized liposomes loaded with methicillin for treating MRSA, with a reported minimum inhibitory concentration of 1.7 µg/mL, well below the free antibiotic dosage needed (5 µg/mL). Cytotoxicity tests with astrocytes and endothelial cells showed a significant reduction of antibiotic cytotoxicity by encapsulating them inside the liposomes. All results obtained for TAT-functionalized liposomes provide evidence that this liposomal system can be a safe, alternative means for treating bacterial meningitis.

TAT-functionalized pH-sensitive liposomes for the treatment of bacterial meningitis

256th National Meeting (2018)

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