C. Bartomeu Garcia, D. Shi, T.J. Webster
Keywords: liposomes, blood brain barrier, meningitis
Summary:Bacterial meningitis is one of the most severe infections that leads to permanent disabilities and brain damage to 20 percent of the population that manage to survive this disease. This brain infection is caused by the inflammation of the meninges and the in-between fluid spaces. If not treated on time, this disease can lead to death. The emergence of drug resistant bacteria has made this disease even more difficult to treat. Such bacteria are not susceptible to any of the current antibiotics, leading to the formation of bacterial biofilms over time. When bacterial biofilms are formed, the ability of antibiotics to treat this disease is further compromised, leading to ineffective treatment and progressed infection. The overuse of antibiotics is another well-known factor to promote the propagation of drug resistant bacteria, creating a need for alternative and more effective treatments to combat this and other infectious diseases. To address this need, we report the use of pH-sensitive liposomes, also called fusogenic liposomes, as drug carriers to target and promote the release of the antibiotic directly inside the bacterial cells. These liposomes present a more fluid lipid bilayer which promote the destabilization of biological cell membranes. Liposomes were prepared by lipid film rehydration and functionalized with TAT peptide using wet chemistry. Liposomes characterization was done by transmission electron microscopy (TEM), presenting sphere shaped particles with a diameter of 100 nm. In addition, these liposomes were functionalized with a cell penetrating peptide, TAT (47-57), to increase their permeability through the blood brain barrier (BBB), which is one of the main challenges for treating brain diseases. This cell penetrating peptide has shown good permeability through the BBB in previous research, making it a critical component to our liposome system. Liposomes were loaded with vancomycin, methicillin and penicillin, the three most commonly used antibiotics to treat this infection. To this end, we report the antibacterial effect of TAT-functionalized and non-functionalized liposomes on three of the main bacteria that cause meningitis, Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli.