Dinitrosyl iron complexes with glutathione incorporated into a collagen matrix as a base for the design of drugs accelerating skin wound healing

Eur J Pharm Sci. 2015 Oct 12:78:8-18. doi: 10.1016/j.ejps.2015.06.002. Epub 2015 Jun 9.

Abstract

Composites of a collagen matrix and dinitrosyl iron complexes with glutathione (DNIC-GS) (in a dose of 4.0 μmoles per item) in the form of spongy sheets (DNIC-Col) were prepared and then topically applied in rat excisional full-thickness skin wound model. The effects of DNIC-Col were studied in comparison with spontaneously healing wounds (SpWH) and wounds treated with collagen sponges (Col) without DNIC-GS. The composites induced statistically and clinically significant acceleration of complete wound closure (21±1 day versus 23±1 day and 26±1 day for DNIC-Col, Col and SpWH, respectively). Histological examination of wound tissues on days 4, 14, 18 and 21 after surgery demonstrated that this improvement was supported by enhanced growth, maturation and fibrous transformation of granulation tissue and earlier epithelization of the injured area in rats treated with DNIC-Col composites benchmarked against Col and SpWH. It is suggested that the positive effect of the new pharmaceutical material on wound healing is based on the release of NO from decomposing DNIC. This effect is believed to be potentiated by the synergy of DNIC and collagen.

Keywords: Collagen; Dinitrosyl iron complex; Nitric oxide; Wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen / administration & dosage*
  • Collagen / chemistry
  • Collagen / therapeutic use
  • Drug Delivery Systems*
  • Glutathione / administration & dosage*
  • Glutathione / chemistry
  • Glutathione / therapeutic use
  • Iron / administration & dosage*
  • Iron / chemistry
  • Iron / therapeutic use
  • Male
  • Nitric Oxide Donors / administration & dosage*
  • Nitric Oxide Donors / chemistry
  • Nitric Oxide Donors / therapeutic use
  • Nitrogen Oxides / administration & dosage*
  • Nitrogen Oxides / chemistry
  • Nitrogen Oxides / therapeutic use
  • Rats
  • Skin / injuries
  • Skin / pathology
  • Wound Healing / drug effects

Substances

  • Nitric Oxide Donors
  • Nitrogen Oxides
  • dinitrosyl iron complex
  • Collagen
  • Iron
  • Glutathione