title: Targeted delivery of vancomycin to Staphylococcus epidermidis biofilms using a fibrinogen-derived peptide.
abstract: This study reports on the use of a fibrinogen-derived peptide for the specific targeting and delivery of vancomycin to Staphylococcus epidermidis biofilms. One method by which S. epidermidis initially adheres to biomaterials uses the plasma protein fibrinogen as an intermediary, where the S. epidermidis surface protein SdrG binds to a short amino acid sequence near the amino terminus of the Bβ chain of fibrinogen. We mimicked this binding interaction and demonstrated the use of a synthetic fibrinogen-based β6-20 peptide to target and deliver vancomycin to S. epidermidis in vitro. The β6-20 peptide was synthesized and labeled with a Nanogold probe, and its targeting capabilities were examined through the use of scanning electron microscopy. The Nanogold component was then replaced by vancomycin, utilizing a flexible, variable length poly(ethylene glycol) linker between the peptide and antibiotic to create the targeted vancomycin products, β6-20-PEG(x) -VAN. Initial binding to surface adherent S. epidermidis was increased in a concentration-dependent manner relative to vancomycin for all equivalent concentrations ≥4 μg/mL, with targeted vancomycin content up to 22.9 times that of vancomycin alone. Retention of the targeted antibiotics was measured after an additional 24-h incubation period, revealing levels 1.3 times that of vancomycin. The results demonstrate the improved targeting and retention of vancomycin within a biofilm due to the incorporation of a specific targeting motif.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hofmann
authors.forename: James M
authors.initials: JM
authors.lastname: Anderson
authors.forename: Roger E
authors.initials: RE
authors.lastname: Marchant
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D016503:Drug Delivery Systems; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000188:drug therapy; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000502:physiology*; D014640:Vancomycin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D014640:Vancomycin; D005340:Fibrinogen