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Wounds. 2019 Feb;31(2):49-54. Epub 2018 Dec 26.

Stability, Activity, and Application of Topical Doxycycline Formulations in a Diabetic Wound Case Study.

Author information

1
Department of Medical Science, McMaster University, Hamilton, Ontario, Canada.
2
Research and Development, Delivra Corp, Charlottetown, Prince Edward Island, Canada.
3
The Mayer Institute, Hamilton, Ontario, Canada.

Abstract

INTRODUCTION:

Tetracycline molecules comprise a group of broad-spectrum antibiotics whose primary mechanism of action is the inhibition of protein synthesis through the binding of the bacterial ribosome. In addition, tetracyclines inhibit matrix metalloproteases (MMPs), a family of zinc-dependent proteases that contribute to tissue remodeling, inflammation, and angiogenesis and are overexpressed in certain pathophysiologies such as diabetic foot ulcers (DFUs).

OBJECTIVE:

This study aims to develop a liquid chromatography and mass spectrometry (LC-MS/MS) doxycycline quantification methodology to facilitate the development of a stable topical doxycycline hyclate (DOXY) formulation as well as evaluate the topical DOXY formulation for the efficacy in MMP-9 inhibition in vitro and in a clinical application of diabetic lower extremity wounds.

MATERIALS AND METHODS:

A simple quantification method utilizing LC-MS/MS was used to develop a topical DOXY formulation, a sample of which was analyzed in stability testing. The formulation was evaluated in vitro for MMP-9 activity using a commercial assay and compared with internal kit controls as well as in a clinical setting for wound healing.

RESULTS:

Two formulations of 2% (w/w) DOXY demonstrated acceptable stability (±10% target concentration) for 70 days when stored at 4°C. Using an in vitro assay of MMP-9 enzyme activity, the 2% DOXY formulation imparted a ~30% decrease in MMP-9 inhibitory potential as compared with the control drug alone (IC₅₀ values 62.92 µM and 48.27 µM, respectively). This topical product was evaluated for clinical utility in a patient with a DFU, and preliminary data suggest this intervention may promote wound healing.

CONCLUSIONS:

In summary, novel DOXY formulations may be stable and biologically active tools amenable to complex wound care.

PMID:
30664497
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