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      Self-assembling ultrashort NSAID-peptide nanosponges: multifunctional antimicrobial and anti-inflammatory materials

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          Abstract

          This paper outlines the design, synthesis and characterisation of innovative NSAID-peptide gelators which demonstrate antimicrobial and anti-inflammatory properties and have potential use as multifunctional materials for biomedical applications.

          Peptide-based materials are receiving significant attention for use within biomedicine due to their high chemical and functional versatility enabling tailoring of their structure to replicate the properties of host tissue and the extracellular matrix. This paper studies the design, synthesis and characterization of NSAID-peptide conjugates. Attachment of NSAIDs to a diphenylalanine–dilysine (FFKK-OH) peptide sequence generates supramolecular hydrogel forming molecules with antimicrobial and anti-inflammatory properties. NSAID-peptides demonstrate broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria implicated in a variety of antimicrobial resistant nosocomial infections including Staphylococcus aureus and Pseudomonas aeruginosa. Naproxen-peptides show particular promise, forming biocompatible nanofibrous viscoelastic hydrogel nanosponges composed of β-sheet secondary structures at low concentrations (0.4% w/v). Conjugation of the peptide motif FFKK-OH to naproxen increases selectivity for COX-2 enzyme, implicated in chronic wound scar-tissue formation. Our findings suggest that ultrashort NSAID-peptides have potential use as multifunctional materials for a range of biomedical applications. This includes as topical agents for treatment of chronic wounds, where a profile of persistent inflammation, pain and the presence of infection has been proven to be detrimental to successful wound repair. This work may also serve as a template for the design of future medical device coatings with tailored antimicrobial and anti-inflammatory properties.

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          Most cited references 57

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          Water gelation by small organic molecules.

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            Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of Gram-positive bacterial infections.

             L Sabath,  G A Pankey (2004)
            The distinction between bactericidal and bacteriostatic agents appears to be clear according to the in vitro definition, but this only applies under strict laboratory conditions and is inconsistent for a particular agent against all bacteria. The distinction is more arbitrary when agents are categorized in clinical situations. The supposed superiority of bactericidal agents over bacteriostatic agents is of little relevance when treating the vast majority of infections with gram-positive bacteria, particularly in patients with uncomplicated infections and noncompromised immune systems. Bacteriostatic agents (e.g., chloramphenicol, clindamycin, and linezolid) have been effectively used for treatment of endocarditis, meningitis, and osteomyelitis--indications that are often considered to require bactericidal activity. Although bacteriostatic/bactericidal data may provide valuable information on the potential action of antibacterial agents in vitro, it is necessary to combine this information with pharmacokinetic and pharmacodynamic data to provide more meaningful prediction of efficacy in vivo. The ultimate guide to treatment of any infection must be clinical outcome.
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              Impaired wound healing.

              Nonhealing wounds represent a significant cause of morbidity and mortality for a large portion of the population. One of the underlying mechanisms responsible for the failure of chronic wounds to heal is an out-of-control inflammatory response that is self-sustaining. Underappreciation of the inherent complexity of the healing wound has led to the failure of monotherapies, with no significant reduction in wound healing times. A model of the inflammatory profile of a nonhealing wound is one in which the equilibrium between synthesis and degradation has been shifted toward degradation. This review summarizes the current information regarding acute wound healing responses as contrasted to the delayed response characteristic of chronic wounds. In addition, some initial complexity theoretical models are proposed to define and explain the underlying pathophysiology.
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                Author and article information

                Journal
                RSCACL
                RSC Advances
                RSC Adv.
                Royal Society of Chemistry (RSC)
                2046-2069
                2016
                2016
                : 6
                : 115
                : 114738-114749
                Article
                10.1039/C6RA20282A
                © 2016
                Product
                Self URI (article page): http://xlink.rsc.org/?DOI=C6RA20282A

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