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Nanostructured Lipid Carrier Gel Formulation of Recombinant Human Thrombomodulin Improve Diabetic Wound Healing by Topical Administration

Recombinant human thrombomodulin (rhTM), an angiogenesis factor, has been demonstrated to stimulate cell proliferation, keratinocyte migration and wound healing. The objective of this study was to develop nanostructured lipid carrier (NLC) formulations encapsulating rhTM for promoting chronic wound...

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Autores principales: Hsueh, Yuan-Shuo, Shyong, Yan-Jye, Yu, Hsiu-Ching, Jheng, Shu-Jhen, Lin, Shang-Wen, Wu, Hua-Lin, Tsai, Jui-Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469737/
https://www.ncbi.nlm.nih.gov/pubmed/34575462
http://dx.doi.org/10.3390/pharmaceutics13091386
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author Hsueh, Yuan-Shuo
Shyong, Yan-Jye
Yu, Hsiu-Ching
Jheng, Shu-Jhen
Lin, Shang-Wen
Wu, Hua-Lin
Tsai, Jui-Chen
author_facet Hsueh, Yuan-Shuo
Shyong, Yan-Jye
Yu, Hsiu-Ching
Jheng, Shu-Jhen
Lin, Shang-Wen
Wu, Hua-Lin
Tsai, Jui-Chen
author_sort Hsueh, Yuan-Shuo
collection PubMed
description Recombinant human thrombomodulin (rhTM), an angiogenesis factor, has been demonstrated to stimulate cell proliferation, keratinocyte migration and wound healing. The objective of this study was to develop nanostructured lipid carrier (NLC) formulations encapsulating rhTM for promoting chronic wound healing. RhTM-loaded NLCs were prepared and characterized. Encapsulation efficiency was more than 92%. The rate of rhTM release from different NLC formulations was influenced by their lipid compositions and was sustained for more than 72 h. Studies on diabetic mouse wound model suggested that rhTM-NLC 1.2 µg accelerated wound healing and was similar to recombinant human epidermal growth factor-NLC (rhEGF-NLC) 20 µg. By incorporating 0.085% carbopol (a highly crosslinked polyacrylic acid polymer) into rhTM NLC, the NLC-gel presented similar particle characteristics, and demonstrated physical stability, sustained release property and stability within 12 weeks. Both rhTM NLC and rhTM NLC-gel improved wound healing of diabetic mice and cell migration of human epidermal keratinocyte cell line (HaCaT) significantly. In comparison with rhTM solution, plasma concentrations of rhTM post applications of NLC and NLC-gel formulations were lower and more sustained in 24 h. The developed rhTM NLC and rhTM NLC-gel formulations are easy to prepare, stable and convenient to apply to the wound with reduced systemic exposure, which may warrant potential delivery systems for the care of chronic wound patients.
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spelling pubmed-84697372021-09-27 Nanostructured Lipid Carrier Gel Formulation of Recombinant Human Thrombomodulin Improve Diabetic Wound Healing by Topical Administration Hsueh, Yuan-Shuo Shyong, Yan-Jye Yu, Hsiu-Ching Jheng, Shu-Jhen Lin, Shang-Wen Wu, Hua-Lin Tsai, Jui-Chen Pharmaceutics Article Recombinant human thrombomodulin (rhTM), an angiogenesis factor, has been demonstrated to stimulate cell proliferation, keratinocyte migration and wound healing. The objective of this study was to develop nanostructured lipid carrier (NLC) formulations encapsulating rhTM for promoting chronic wound healing. RhTM-loaded NLCs were prepared and characterized. Encapsulation efficiency was more than 92%. The rate of rhTM release from different NLC formulations was influenced by their lipid compositions and was sustained for more than 72 h. Studies on diabetic mouse wound model suggested that rhTM-NLC 1.2 µg accelerated wound healing and was similar to recombinant human epidermal growth factor-NLC (rhEGF-NLC) 20 µg. By incorporating 0.085% carbopol (a highly crosslinked polyacrylic acid polymer) into rhTM NLC, the NLC-gel presented similar particle characteristics, and demonstrated physical stability, sustained release property and stability within 12 weeks. Both rhTM NLC and rhTM NLC-gel improved wound healing of diabetic mice and cell migration of human epidermal keratinocyte cell line (HaCaT) significantly. In comparison with rhTM solution, plasma concentrations of rhTM post applications of NLC and NLC-gel formulations were lower and more sustained in 24 h. The developed rhTM NLC and rhTM NLC-gel formulations are easy to prepare, stable and convenient to apply to the wound with reduced systemic exposure, which may warrant potential delivery systems for the care of chronic wound patients. MDPI 2021-09-02 /pmc/articles/PMC8469737/ /pubmed/34575462 http://dx.doi.org/10.3390/pharmaceutics13091386 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hsueh, Yuan-Shuo
Shyong, Yan-Jye
Yu, Hsiu-Ching
Jheng, Shu-Jhen
Lin, Shang-Wen
Wu, Hua-Lin
Tsai, Jui-Chen
Nanostructured Lipid Carrier Gel Formulation of Recombinant Human Thrombomodulin Improve Diabetic Wound Healing by Topical Administration
title Nanostructured Lipid Carrier Gel Formulation of Recombinant Human Thrombomodulin Improve Diabetic Wound Healing by Topical Administration
title_full Nanostructured Lipid Carrier Gel Formulation of Recombinant Human Thrombomodulin Improve Diabetic Wound Healing by Topical Administration
title_fullStr Nanostructured Lipid Carrier Gel Formulation of Recombinant Human Thrombomodulin Improve Diabetic Wound Healing by Topical Administration
title_full_unstemmed Nanostructured Lipid Carrier Gel Formulation of Recombinant Human Thrombomodulin Improve Diabetic Wound Healing by Topical Administration
title_short Nanostructured Lipid Carrier Gel Formulation of Recombinant Human Thrombomodulin Improve Diabetic Wound Healing by Topical Administration
title_sort nanostructured lipid carrier gel formulation of recombinant human thrombomodulin improve diabetic wound healing by topical administration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469737/
https://www.ncbi.nlm.nih.gov/pubmed/34575462
http://dx.doi.org/10.3390/pharmaceutics13091386
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