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Composite Hydrogel Formulations of Stratifin to Control MMP-1 Expression in Dermal Fibroblasts

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Abstract

Purpose

Stratifin is a potent anti-fibrogenic factor that stimulates the expression of matrix metalloproteinase-1 (MMP-1) in dermal fibroblasts. The propose of this work was to develop a controlled release delivery system for stratifin that can be applied at the time of wound closure to release stratifin and stimulate the expression of MMP-1 in a sustained manner over the late stages of wound healing (after 3 days).

Methods

Stratifin was complexed to chitosan particles, which were then encapsulated in PLGA microspheres and blended into crosslinked hyaluronic acid films. In vitro release was assessed using fluorescent-tagged stratifin, cytotoxity by MTT assay and bioactivity by measuring the levels of MMP-1 expression in cultured fibroblasts.

Results

The release of stratifin was delayed for 3 days and then controlled for 30 days so that 60% of the total stratifin loaded was released. The released protein significantly stimulated the expression of MMP-1 in cultured fibroblasts without compromising cell viability. By complexing to chitosan, the initial burst release was reduced, so that only 5% of stratifin was released in 3 days.

Conclusion

This stratifin delivery sytem has the potential to be used as an anti-fibrogenic factor-associated wound insert for improving post-surgical scarring in closed wound.

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ACKNOWLEDGMENTS

This work was supported by CIHR and BC Professional Firefighter’s fund. Special thanks to Dr. Abdi Ghaffari (Burn & wound healing laboratory) for his expertise in preparing recombinant stratifin and also Derrick Horne (Bioimaging facility at the University of British Columbia) for his assistance in scanning electron microscopy.

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Authors and Affiliations

  1. BC Professional Fire Fighters’ Burn & Wound Healing Research Lab. Jack Bell Research Center, 2660 Oak St., Vancouver, B.C. V6H 3Z6, Canada

    Elham Rahmani-Neishaboor & Aziz Ghahary

  2. Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, B.C. V6T 1Z3, Canada

    John Jackson & Helen Burt

Authors
  1. Elham Rahmani-Neishaboor
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  2. John Jackson
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  3. Helen Burt
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  4. Aziz Ghahary
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Correspondence to Aziz Ghahary.

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Rahmani-Neishaboor, E., Jackson, J., Burt, H. et al. Composite Hydrogel Formulations of Stratifin to Control MMP-1 Expression in Dermal Fibroblasts. Pharm Res 26, 2002–2014 (2009). https://doi.org/10.1007/s11095-009-9916-0

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  • DOI: https://doi.org/10.1007/s11095-009-9916-0

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