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Published on: May 24, 2024
Controlled release of repifermin from polyelectrolyte complexes stimulates endothelial cell proliferation
1Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA.
Journal of Pharmaceutical Sciences
|April 22, 2008
Summary
This study stabilizes Repifermin, a growth factor for wound healing, using polyelectrolyte complexes. This controlled release formulation enhances therapeutic efficacy and protein stability for improved wound repair.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Protein Engineering
Background:
- Therapeutic growth factors often require controlled release due to narrow therapeutic indices and short half-lives.
- Repifermin (fibroblast growth factor-10/keratinocyte growth factor-2) shows wound healing potential but is a labile protein, challenging for controlled release formulation.
Purpose of the Study:
- To develop a stabilized, controlled-release formulation for Repifermin.
- To enhance the therapeutic efficacy and stability of Repifermin for wound healing applications.
Main Methods:
- Repifermin was stabilized by exploiting its heparin-binding motif with dextran sulfate, confirmed by spectroscopic techniques.
- Polyelectrolyte complexes (PECs) of ~250 nm were formed using Repifermin-bound dextran sulfate and polycations (chitosan, poly-L-lysine, polyethylenimine).
- Protein entrapment efficiency, release kinetics (>10 days), and mitogenic activity on endothelial cells were evaluated.
Main Results:
- Dextran sulfate increased Repifermin's unfolding temperature by ~10°C, indicating enhanced stability.
- Polyelectrolyte complexes entrapped Repifermin with 70-80% efficiency.
- Controlled release over 10 days was achieved, with significantly enhanced mitogenic activity compared to free Repifermin.
Conclusions:
- Polyelectrolyte complexes effectively stabilize and control the release of Repifermin.
- This formulation strategy enhances the biological activity of Repifermin, offering a promising approach for advanced wound healing therapies.

