title: Nanotechnology approaches for antibacterial drug delivery: Preparation and microbiological evaluation of fusogenic liposomes carrying fusidic acid.
abstract: Many antibacterial drugs have some difficulty passing through the bacterial cell membrane, especially if they have a high molecular weight or large spatial structure. Consequently, intrinsic resistance is shown by some bacterial strains. Reduced cell membrane permeability is one of the mechanisms of resistance known for fusidic acid (FUS), a bacteriostatic steroidal compound with activity limited to Gram-positive bacteria. Moreover, the lipophilic character of FUS has been shown to cause drug retention inside the bilayers of cell membranes, preventing its diffusion towards target sites inside the cytoplasm. Targeting antimicrobial agents by means of liposomes may be a valid strategy in the treatment of infections refractory to conventional routes of antimicrobial treatment. On this basis, loading of FUS in fusogenic liposomes (FLs) was planned in this study. Fusogenic small unilamellar vesicles loaded with FUS were produced to evaluate their influence on improving the cell penetration and antibacterial activity of the antibiotic. The produced carriers were technologically characterised and were subjected to an in vitro microbiological assay against several strains of Gram-negative and Gram-positive bacteria. The experimental results showed that encapsulating FUS in a liposomal carrier can improve antimicrobial efficacy and reduce the effective concentration required, probably through putative mechanisms of increased diffusion through the bacterial cell membrane. In fact, whilst free FUS was active only on the tested Gram-positive strains, incubation of FUS-loaded FLs exhibited growth inhibitory activity both against Gram-positive and Gram-negative strains. The lowest MICs were obtained against Staphylococcus epidermidis (≤0.15 μg/mL) and Acinetobacter baumannii (37.5 μg/mL) clinical strains.
authors: Section of Microbiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors: Daria
authors: D
authors: Nicolosi
authors: Section of Pharmaceutical Technology, Department of Drug Sciences, University of Catania, Catania, Italy.
authors: Sarha
authors: S
authors: Cupri
authors: Section of Microbiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors: Carlo
authors: C
authors: Genovese
authors: Section of Microbiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors: Gianna
authors: G
authors: Tempera
authors: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors: Roberto
authors: R
authors: Mattina
authors: Section of Pharmaceutical Technology, Department of Drug Sciences, University of Catania, Catania, Italy; NANO-i, Research Centre for Ocular Nanotechnology, University of Catania, Catania, Italy. Electronic address: r.pignatello@unict.it.
authors: Rosario
authors: R
authors: Pignatello
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D016503:Drug Delivery Systems; D005672:Fusidic Acid / Q000378:metabolism*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008081:Liposomes / Q000378:metabolism*; D036103:Nanotechnology / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D008081:Liposomes; D005672:Fusidic Acid
keywords: Acinetobacter baumannii; Fusogenic liposomes; Gram-negative bacteria; Gram-positive bacteria; SUVET