Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy

Jun-Pil Jee1,*, Rudra Pangeni2,*, Saurav Kumar Jha,2 Youngro Byun,3 Jin Woo Park21College of Pharmacy, Chosun University, Gwangju 61452, Republic of Korea; 2College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam 58554, Republic of Korea; 3Department...

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Autores principales:	Jee JP, Pangeni R, Jha SK, Byun Y, Park JW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Diabetic wound-healing topical hydrogel highly skin-permeable growth factors quercetin 1-bromo perfluorooctane oxygen delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/01d66642eb3e4354b124dc48496c7b8f
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spelling	oai:doaj.org-article:01d66642eb3e4354b124dc48496c7b8f2021-12-02T09:32:15ZPreparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy1178-2013https://doaj.org/article/01d66642eb3e4354b124dc48496c7b8f2019-07-01T00:00:00Zhttps://www.dovepress.com/preparation-and-in-vivo-evaluation-of-a-topical-hydrogel-system-incorp-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jun-Pil Jee1,, Rudra Pangeni2,, Saurav Kumar Jha,2 Youngro Byun,3 Jin Woo Park21College of Pharmacy, Chosun University, Gwangju 61452, Republic of Korea; 2College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam 58554, Republic of Korea; 3Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea*These authors contributed equally to this workPurpose: We created and evaluated an enhanced topical delivery system featuring a combination of highly skin-permeable growth factors (GFs), quercetin (QCN), and oxygen; these synergistically accelerated re-epithelialization and granulation tissue formation of/in diabetic wounds by increasing the levels of GFs and antioxidants, and the oxygen partial pressure, at the wound site.Methods: To enhance the therapeutic effects of exogenous administration of GFs for the treatment of diabetic wounds, we prepared highly skin-permeable GF complexes comprised of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), platelet-derived growth factor-A (PDGF-A), and basic fibroblast growth factor (bFGF), genetically attached, via the N-termini, to a low-molecular-weight protamine (LMWP) to form LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, and LMWP-bFGF, respectively. Furthermore, quercetin (QCN)- and oxygen-carrying 1-bromoperfluorooctane (PFOB)-loaded nanoemulsions (QCN-NE and OXY-PFOB-NE) were developed to improve the topical delivery of QCN and oxygen, respectively. After confirming the enhanced penetration of LMWP-GFs, QCN-NE, and oxygen delivered from OXY-PFOB-NE across human epidermis, we evaluated the effects of combining LMWP-GFs, QCN-NE, and OXY-PFOB-NE on proliferation of keratinocytes and fibroblasts, and the chronic wound closure rate of a diabetic mouse model.Results: The optimal ratios of LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, LMWP-bFGF, QCN-NE, and OXY-PFOB-NE were 1, 1, 0.02, 0.02, 0.2, and 60, respectively. Moreover, a Carbopol hydrogel containing LMWP-GFs, QCN-NE, and OXY-PFOB-NE (LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL) significantly improved scratch-wound recovery of keratinocytes and fibroblasts in vitro compared to that afforded by hydrogels containing each component alone. LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL significantly accelerated wound-healing in a diabetic mouse model, decreasing wound size by 54 and 35% compared to the vehicle and LMWP-GFs, respectively.Conclusion: LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL synergistically accelerated the healing of chronic wounds, exerting both rapid and prolonged effects.Keywords: diabetic wound-healing, topical hydrogel, highly skin-permeable growth factors, quercetin, 1-bromoperfluorooctane, oxygen deliveryJee JPPangeni RJha SKByun YPark JWDove Medical PressarticleDiabetic wound-healingtopical hydrogelhighly skin-permeable growth factorsquercetin1-bromo perfluorooctaneoxygen deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 5449-5475 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diabetic wound-healing topical hydrogel highly skin-permeable growth factors quercetin 1-bromo perfluorooctane oxygen delivery Medicine (General) R5-920
spellingShingle	Diabetic wound-healing topical hydrogel highly skin-permeable growth factors quercetin 1-bromo perfluorooctane oxygen delivery Medicine (General) R5-920 Jee JP Pangeni R Jha SK Byun Y Park JW Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy
description	Jun-Pil Jee1,, Rudra Pangeni2,, Saurav Kumar Jha,2 Youngro Byun,3 Jin Woo Park21College of Pharmacy, Chosun University, Gwangju 61452, Republic of Korea; 2College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam 58554, Republic of Korea; 3Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea*These authors contributed equally to this workPurpose: We created and evaluated an enhanced topical delivery system featuring a combination of highly skin-permeable growth factors (GFs), quercetin (QCN), and oxygen; these synergistically accelerated re-epithelialization and granulation tissue formation of/in diabetic wounds by increasing the levels of GFs and antioxidants, and the oxygen partial pressure, at the wound site.Methods: To enhance the therapeutic effects of exogenous administration of GFs for the treatment of diabetic wounds, we prepared highly skin-permeable GF complexes comprised of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), platelet-derived growth factor-A (PDGF-A), and basic fibroblast growth factor (bFGF), genetically attached, via the N-termini, to a low-molecular-weight protamine (LMWP) to form LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, and LMWP-bFGF, respectively. Furthermore, quercetin (QCN)- and oxygen-carrying 1-bromoperfluorooctane (PFOB)-loaded nanoemulsions (QCN-NE and OXY-PFOB-NE) were developed to improve the topical delivery of QCN and oxygen, respectively. After confirming the enhanced penetration of LMWP-GFs, QCN-NE, and oxygen delivered from OXY-PFOB-NE across human epidermis, we evaluated the effects of combining LMWP-GFs, QCN-NE, and OXY-PFOB-NE on proliferation of keratinocytes and fibroblasts, and the chronic wound closure rate of a diabetic mouse model.Results: The optimal ratios of LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, LMWP-bFGF, QCN-NE, and OXY-PFOB-NE were 1, 1, 0.02, 0.02, 0.2, and 60, respectively. Moreover, a Carbopol hydrogel containing LMWP-GFs, QCN-NE, and OXY-PFOB-NE (LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL) significantly improved scratch-wound recovery of keratinocytes and fibroblasts in vitro compared to that afforded by hydrogels containing each component alone. LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL significantly accelerated wound-healing in a diabetic mouse model, decreasing wound size by 54 and 35% compared to the vehicle and LMWP-GFs, respectively.Conclusion: LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL synergistically accelerated the healing of chronic wounds, exerting both rapid and prolonged effects.Keywords: diabetic wound-healing, topical hydrogel, highly skin-permeable growth factors, quercetin, 1-bromoperfluorooctane, oxygen delivery
format	article
author	Jee JP Pangeni R Jha SK Byun Y Park JW
author_facet	Jee JP Pangeni R Jha SK Byun Y Park JW
author_sort	Jee JP
title	Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy
title_short	Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy
title_full	Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy
title_fullStr	Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy
title_full_unstemmed	Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy
title_sort	preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/01d66642eb3e4354b124dc48496c7b8f
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Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy

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