Vesicular Lipid Nanoparticles (Liposomes) for the Treatment of Medical Device Infections
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Vesicular Lipid Nanoparticles (Liposomes) for the Treatment of Medical Device Infections Erik Taylor1, Anubhav Kaviratna2, Rinti Banerjee2, and Thomas J. Webster1 1
School of Engineering and Department of Orthopaedics, Brown University
Providence, RI 02917, USA 2
Department of Biosciences and Bioengineering, Indian Institute of Technology
Mumbai, 400076, India Abstract Liposomes (a phospholipid bi-layer which can be formulated to contain drugs or other reagents) composed of endogenous phospholipid dipalmitoylphosphatidylcholine (DPPC) in combination with dioleoylphosphatidylethanolamine (DOPE), lauric acid, and silver sulfadiazine were made into vesicular nanoparticles in this study using an optimized extrusion technique. Liposomes were then tested for antibacterial activity against a range of bacteria species including Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Bacillus subtilis (all are relevant human pathogens known to infect implants) and were also challenged to prevent the growth of adherent biofilms (a robust slimy extracellular matrix) through an in vitro assay relevant to device related infections. It was found that all liposomes reduced bacterial growth, and, most importantly, liposomes containing DPPC and DOPE reduced biofilm formation better than the commercially available antibiotic silver sulfadiazine. These results indicated for the first time that such liposomes might be a better approach to prevent device related infections. Introduction and Statement of the Problem Implant failure from infection is often mediated by the formation of a biofilm (that is, a matrixenclosed film associated with bacterial communities) which is resistant to antibiotic treatment and must be physically removed before infection can be resolved [1]. Biofilms form a sticky matrix which encapsulates the bacteria and forms a mechanically robust adhesion to an underlying substrate. Biofilm bacteria are resistant to antibiotic treatment due to genetic tolerance or slow growth rates, therefore, infections are recalcitrant without prolonged treatment (which promotes the emergence of antibiotic resistant strains) or removal of the device which requires tissue washout and device removal with intense antibiotic treatment followed by prolonged oral prescription antibiotics (which promotes the emergence of antibiotic resistant strains) [2]. These procedures are expensive to the patient in terms of extra cost and decreased quality of life. Clearly, new materials or procedures are needed to reduce such infections. Compounds which are specifically designed to prevent the formation of biofilms on implant devices might be a better approach to stop device related bacterial infections. Lipid compounds are one potential treatment of biofilm or antibiotic resistant infection. It is interesting to note here that a large composition of human tissue abscess, nasal fluid, lung surfactant, and breast milk are composed of lipid compounds with antibacterial activity, which implies some role in human innate immunity (one way
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