title: Development of an insect metalloproteinase inhibitor drug carrier system for application in chronic wound infections.
abstract: OBJECTIVE
  The insect metalloproteinase inhibitor (IMPI) represents the first peptide capable of inhibiting virulence-mediating microbial M4-metalloproteinases and is promising as a therapeutic. The purpose of this study was to develop a suitable drug carrier system for the IMPI drug to enable treatment of chronic wound infections. Specifically, we studied on poloxamer 407 hydrogels, examining the influence of several additives and preservatives on the rheological parameters of the hydrogels, the bioactivity and release of IMPI.
  
  
  METHODS
  The rheological characterisation of the hydrogel was performed by oscillatory measurements. The bioactivity of IMPI was evaluated in a Casein fluoresence quenching assay.
  
  
  RESULTS
  In this study, a suitable application form for the dermal treatment of chronic wound infections with IMPI was designed. The influences of poloxamer 407 concentration and various additives on the viscoelastic properties and preservation of a thermosensitive hydrogel were investigated. The incorporation of the precursor drug IMPI-gluthathione-s-transferase (GST) in the hydrogel had no influence on the rheological characteristics and will be released. The bioactivity of IMPI-GST is not influenced by the hydrogel and remains constant over 4 weeks of storage.
  
  
  CONCLUSIONS
  This study reports the development of a poloxamer hydrogel as a suitable carrier system for the application of IMPI.
authors.affiliation: Institute of Bioprocess Engineering and Pharmaceutical Technology, Technische Hochschule Mittelhessen - University of Applied Sciences, Giessen, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Eisenhardt
authors.affiliation: Institute of Bioprocess Engineering and Pharmaceutical Technology, Technische Hochschule Mittelhessen - University of Applied Sciences, Giessen, Germany.
authors.forename: Dorota
authors.initials: D
authors.lastname: Dobler
authors.affiliation: Institute of Bioprocess Engineering and Pharmaceutical Technology, Technische Hochschule Mittelhessen - University of Applied Sciences, Giessen, Germany.
authors.forename: Peggy
authors.initials: P
authors.lastname: Schlupp
authors.affiliation: Institute of Bioprocess Engineering and Pharmaceutical Technology, Technische Hochschule Mittelhessen - University of Applied Sciences, Giessen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmidts
authors.affiliation: Department of Bio-Resources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Giessen, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Salzig
authors.affiliation: Department of Bio-Resources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Vilcinskas
authors.affiliation: Institute of Bioprocess Engineering and Pharmaceutical Technology, Technische Hochschule Mittelhessen - University of Applied Sciences, Giessen, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Salzig
authors.affiliation: Institute of Bioprocess Engineering and Pharmaceutical Technology, Technische Hochschule Mittelhessen - University of Applied Sciences, Giessen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Czermak
authors.affiliation: Institute for Pharmaceutical Chemistry, Philipps University, Marburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Keusgen
authors.affiliation: Institute of Bioprocess Engineering and Pharmaceutical Technology, Technische Hochschule Mittelhessen - University of Applied Sciences, Giessen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Runkel
mesh_terms: D000818:Animals; D002364:Caseins / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry; D005453:Fluorescence; D005982:Glutathione Transferase / Q000737:chemistry; D020100:Hydrogels; D019476:Insect Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D009036:Moths; D020442:Poloxamer / Q000737:chemistry*; D012212:Rheology; D013997:Time Factors; D055682:Viscoelastic Substances; D014946:Wound Infection / Q000188:drug therapy*
chemical_list: D002364:Caseins; D004337:Drug Carriers; D005079:Excipients; D020100:Hydrogels; D019476:Insect Proteins; D061965:Matrix Metalloproteinase Inhibitors; D055682:Viscoelastic Substances; D020442:Poloxamer; D005982:Glutathione Transferase
keywords: hydrogel; insect metalloproteinase inhibitor IMPI; microbial metalloproteinase; poloxamer 407; protein drug delivery; wound dressing