Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma

Yasmeen Ezzeldeen,1 Shady Swidan,1,2 Aliaa ElMeshad,3,4 Aya Sebak5 1Department of Pharmaceutics, Faculty of Pharmacy, The British University in Egypt (BUE), El-Sherouk City, Cairo, 11837, Egypt; 2The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egyp...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ezzeldeen Y, Swidan S, ElMeshad A, Sebak A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	honokiol melanoma transfersomes heating method tumor microenvironment immunosuppressive stem-like cell Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/206e95dd9cb94548bc66d75645313157
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:206e95dd9cb94548bc66d75645313157
record_format	dspace
spelling	oai:doaj.org-article:206e95dd9cb94548bc66d756453131572021-12-02T18:45:38ZGreen Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma1178-2013https://doaj.org/article/206e95dd9cb94548bc66d756453131572021-08-01T00:00:00Zhttps://www.dovepress.com/green-synthesized-honokiol-transfersomes-relieve-the-immunosuppressive-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Yasmeen Ezzeldeen,1 Shady Swidan,1,2 Aliaa ElMeshad,3,4 Aya Sebak5 1Department of Pharmaceutics, Faculty of Pharmacy, The British University in Egypt (BUE), El-Sherouk City, Cairo, 11837, Egypt; 2The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt; 4Department of Bio Nano, Faculty of Nanotechnology for Postgraduate Studies, Cairo University, El-Sheikh Zayed, Giza, 12588, Egypt; 5Department of Pharmaceutical Technology, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo, EgyptCorrespondence: Shady Swidan Tel +20 10-0221-1048Email shady.swidan@bue.edu.egAliaa ElMeshad Tel +20 10-0010-1551Email aliaa.elmeshad@pharma.cu.edu.egBackground: Honokiol (HK) is a natural bioactive compound with proven antineoplastic properties against melanoma. However, it shows very low bioavailability when administered orally. Alternatively, topical administration may offer a promising route. The objective of the current study was to fabricate HK transfersomes (HKTs) for topical treatment of melanoma. As an ultradeformable carrier system, transfersomes can overcome the physiological barriers to topical treatment of melanoma: the stratum corneum and the anomalous tumor microenvironment. Moreover, the immunomodulatory and stemness-regulation roles of HKTs were the main interest of this study.Methods: TFs were prepared using the modified scalable heating method. A three-factor, three-level Box–Behnken design was utilized for the optimization of the process and formulation variables. Intracellular uptake and cytotoxicity of HKTs were evaluated in nonactivated and stromal cell–activated B16F10 melanoma cells to investigate the influence of the complex tumor microenvironment on the efficacy of HK. Finally, ELISA and Western blot were performed to evaluate the expression levels of TGF-β and clusters of differentiation (CD47 and CD133, respectively).Results: The optimized formula exhibited a mean size of 190 nm, highly negative surface charge, high entrapment efficiency, and sustained release profile. HKTs showed potential to alleviate the immunosuppressive characteristics of B16F10 melanoma in vitro via downregulation of TGF-β signaling. In addition, HKTs reduced expression of the “do not eat me” signal — CD47. Moreover, HKTs possessed additional interesting potential to reduce the expression of the stem-like cell marker CD133. These outcomes were boosted upon combination with metformin, an antihyperglycemic drug recently reported to possess different functions in cancer, while combination with collagenase, an extracellular matrix–depleting enzyme, produced detrimental effects.Conclusion: HKTs represent a promising scalable formulation for treatment of the aggressive B16F10 melanoma, which is jam-packed with immunosuppressive and stem-like cell markers.Keywords: honokiol, melanoma, transfersomes, heating method, tumor microenvironment, immunosuppressive, stem-like cellEzzeldeen YSwidan SElMeshad ASebak ADove Medical Pressarticlehonokiolmelanomatransfersomesheating methodtumor microenvironmentimmunosuppressivestem-like cellMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 5693-5712 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	honokiol melanoma transfersomes heating method tumor microenvironment immunosuppressive stem-like cell Medicine (General) R5-920
spellingShingle	honokiol melanoma transfersomes heating method tumor microenvironment immunosuppressive stem-like cell Medicine (General) R5-920 Ezzeldeen Y Swidan S ElMeshad A Sebak A Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma
description	Yasmeen Ezzeldeen,1 Shady Swidan,1,2 Aliaa ElMeshad,3,4 Aya Sebak5 1Department of Pharmaceutics, Faculty of Pharmacy, The British University in Egypt (BUE), El-Sherouk City, Cairo, 11837, Egypt; 2The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt; 4Department of Bio Nano, Faculty of Nanotechnology for Postgraduate Studies, Cairo University, El-Sheikh Zayed, Giza, 12588, Egypt; 5Department of Pharmaceutical Technology, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo, EgyptCorrespondence: Shady Swidan Tel +20 10-0221-1048Email shady.swidan@bue.edu.egAliaa ElMeshad Tel +20 10-0010-1551Email aliaa.elmeshad@pharma.cu.edu.egBackground: Honokiol (HK) is a natural bioactive compound with proven antineoplastic properties against melanoma. However, it shows very low bioavailability when administered orally. Alternatively, topical administration may offer a promising route. The objective of the current study was to fabricate HK transfersomes (HKTs) for topical treatment of melanoma. As an ultradeformable carrier system, transfersomes can overcome the physiological barriers to topical treatment of melanoma: the stratum corneum and the anomalous tumor microenvironment. Moreover, the immunomodulatory and stemness-regulation roles of HKTs were the main interest of this study.Methods: TFs were prepared using the modified scalable heating method. A three-factor, three-level Box–Behnken design was utilized for the optimization of the process and formulation variables. Intracellular uptake and cytotoxicity of HKTs were evaluated in nonactivated and stromal cell–activated B16F10 melanoma cells to investigate the influence of the complex tumor microenvironment on the efficacy of HK. Finally, ELISA and Western blot were performed to evaluate the expression levels of TGF-β and clusters of differentiation (CD47 and CD133, respectively).Results: The optimized formula exhibited a mean size of 190 nm, highly negative surface charge, high entrapment efficiency, and sustained release profile. HKTs showed potential to alleviate the immunosuppressive characteristics of B16F10 melanoma in vitro via downregulation of TGF-β signaling. In addition, HKTs reduced expression of the “do not eat me” signal — CD47. Moreover, HKTs possessed additional interesting potential to reduce the expression of the stem-like cell marker CD133. These outcomes were boosted upon combination with metformin, an antihyperglycemic drug recently reported to possess different functions in cancer, while combination with collagenase, an extracellular matrix–depleting enzyme, produced detrimental effects.Conclusion: HKTs represent a promising scalable formulation for treatment of the aggressive B16F10 melanoma, which is jam-packed with immunosuppressive and stem-like cell markers.Keywords: honokiol, melanoma, transfersomes, heating method, tumor microenvironment, immunosuppressive, stem-like cell
format	article
author	Ezzeldeen Y Swidan S ElMeshad A Sebak A
author_facet	Ezzeldeen Y Swidan S ElMeshad A Sebak A
author_sort	Ezzeldeen Y
title	Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma
title_short	Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma
title_full	Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma
title_fullStr	Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma
title_full_unstemmed	Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma
title_sort	green synthesized honokiol transfersomes relieve the immunosuppressive and stem-like cell characteristics of the aggressive b16f10 melanoma
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/206e95dd9cb94548bc66d75645313157
work_keys_str_mv	AT ezzeldeeny greensynthesizedhonokioltransfersomesrelievetheimmunosuppressiveandstemlikecellcharacteristicsoftheaggressiveb16f10melanoma AT swidans greensynthesizedhonokioltransfersomesrelievetheimmunosuppressiveandstemlikecellcharacteristicsoftheaggressiveb16f10melanoma AT elmeshada greensynthesizedhonokioltransfersomesrelievetheimmunosuppressiveandstemlikecellcharacteristicsoftheaggressiveb16f10melanoma AT sebaka greensynthesizedhonokioltransfersomesrelievetheimmunosuppressiveandstemlikecellcharacteristicsoftheaggressiveb16f10melanoma
_version_	1718377668078993408

Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma

Ejemplares similares