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A temporal gene delivery system based on fibrin microspheres.

Mangesh M Kulkarni1, Udo Greiser, Timothy O'Brien

  • 1Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.

Molecular Pharmaceutics
|December 22, 2010
PubMed
Summary

Fibrin microspheres effectively encapsulate DNA complexes, enhancing gene delivery capacity within fibrin scaffolds. This approach enables controlled, extended release for potential therapeutic applications.

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Area of Science:

  • Biomaterials Science
  • Gene Therapy
  • Tissue Engineering

Background:

  • Nonviral gene delivery systems combining scaffolds and liposomes offer potential for safe and effective gene therapy.
  • Current limitations include the DNA loading capacity of traditional scaffolds like fibrin.
  • Fibrin microspheres present a novel strategy to overcome these capacity limitations.

Purpose of the Study:

  • To investigate the feasibility of using fibrin microspheres to enhance gene delivery capacity.
  • To develop a "fibrin in fibrin" temporal release system for sustained gene delivery.
  • To assess the structural and functional integrity of DNA delivered via fibrin microspheres.

Main Methods:

  • Fabrication of fibrin microspheres encapsulating DNA-liposome complexes (lipoplexes).
  • Assessment of DNA structural integrity using gel electrophoresis.
  • In vivo evaluation of functional gene delivery and therapeutic effect using endothelial nitric oxide synthase (eNOS) in a rabbit ear ulcer model.

Main Results:

  • Fibrin microspheres successfully encapsulated lipoplexes, maintaining DNA structural integrity.
  • Demonstrated successful in vivo delivery and functional integrity of eNOS gene, evidenced by an angiogenic effect.
  • Fibrin microspheres exhibited differential degradation and DNA release compared to the bulk fibrin scaffold.

Conclusions:

  • Fibrin microspheres are a viable method for increasing the gene delivery capacity of fibrin scaffolds.
  • This technology can be integrated into a "fibrin in fibrin" system for temporal control of gene release.
  • The findings support the potential of fibrin microspheres as a component in advanced gene delivery systems.