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Layer-by-Layer Thin Films for Co-Delivery of TGF-β siRNA and Epidermal Growth Factor to Improve Excisional Wound Healing

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Abstract

The major challenge with treatment of dermal wounds is accelerating healing process, while preventing the scar formation. Herein, we have fabricated layer-by-layer (LbL) polyelectrolyte multilayer films containing epidermal growth factor (EGF) and TGF-β siRNA to improve excisional wound healing and decrease scar formation. The chitosan and sodium alginate LbL thin films showed 13.0 MPa tensile strength and 2.22 N/cm2 skin adhesion strength. The LbL thin films were found to be cytocompatible, where A431 epidermal keratinocytes adhered to the film and showed 86.2 ± 0.8% cell growth compared with cells cultured in the absence of LbL thin film. In contrast, LbL thin film did not promote the Escherichia coli and Staphylococcus aureus bacterial colony formation. In a C57BL/6 mouse excisional wound model, application of LbL thin films containing TGF-β siRNA significantly (p < 0.05) reduced the TGF-β protein expression and collagen production. The LbL thin films containing EGF showed improved wound contraction (<9 days post excision). The co-delivery of TGF-β siRNA and EGF using LbL thin films resulted in accelerated wound healing and decreased collagen deposition. Furthermore, the LbL thin films with TGF-β siRNA and EGF combination showed greater reepithelialization. Taken together, we have successfully demonstrated the co-delivery of TGF-β siRNA and EGF peptide using LbL thin films to promote wound healing and decrease scar formation.

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Acknowledgments

This work was financially supported by a grant from the Department of Science and Technology, Government of India under SERB-Young Scientist award (SERB/F/1260/2012-13). Texture analyzer and multimode plate reader were procured using a grant from Department of Science and Technology—fund for improvement of science and technology infrastructure (DST FIST). PK Mandapalli received senior research fellowship from the Council of Scientific and Industrial Research to pursue doctoral studies.

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Correspondence to Venkata Vamsi Krishna Venuganti.

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Mandapalli, P.K., Labala, S., Jose, A. et al. Layer-by-Layer Thin Films for Co-Delivery of TGF-β siRNA and Epidermal Growth Factor to Improve Excisional Wound Healing. AAPS PharmSciTech 18, 809–820 (2017). https://doi.org/10.1208/s12249-016-0571-6

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