Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma

Mahmoud MA Elsayed,1 Mahmoud E Mostafa,2 Eman Alaaeldin,2,3 Hatem AA Sarhan,2 Montaser ShA Shaykoon,4 Shady Allam,5 Ahmed RH Ahmed,6 Bakheet EM Elsadek7 1Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University, Sohag, Egypt; 2Department of Pharmaceutics, Faculty of P...

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Autores principales:	Elsayed MMA, Mostafa ME, Alaaeldin E, Sarhan HAA, Shaykoon MS, Allam S, Ahmed ARH, Elsadek BEM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	carbon nanotubes sorafenib dena hepatocellular carcinoma microcapsules Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3489a32513b34e969844f918bb4d15a3
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spelling	oai:doaj.org-article:3489a32513b34e969844f918bb4d15a32021-12-02T06:41:24ZDesign And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma1178-2013https://doaj.org/article/3489a32513b34e969844f918bb4d15a32019-10-01T00:00:00Zhttps://www.dovepress.com/design-and-characterisation-of-novel-sorafenib-loaded-carbon-nanotubes-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mahmoud MA Elsayed,1 Mahmoud E Mostafa,2 Eman Alaaeldin,2,3 Hatem AA Sarhan,2 Montaser ShA Shaykoon,4 Shady Allam,5 Ahmed RH Ahmed,6 Bakheet EM Elsadek7 1Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University, Sohag, Egypt; 2Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt; 3Department of Clinical Pharmacy, Deraya University, Minia, Egypt; 4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt; 5Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt; 6Department of Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt; 7Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, EgyptCorrespondence: Bakheet EM ElsadekBiochemistry and Molecular Biology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, P. O. Box 71524, Assiut, EgyptTel +201110596270Email bakheet.elkot@azhar.edu.egPurpose: Over the past 30 years, no consistent survival benefits have been recorded for anticancer agents of advanced hepatocellular carcinoma (HCC), except for the multikinase inhibitor sorafenib (Nexavar®), which clinically achieves only &sim;3 months overall survival benefit. This modest benefit is attributed to limited aqueous solubility, slow dissolution rate and, consequently, limited absorption from the gastrointestinal tract. Thus, novel formulation modalities are in demand to improve the bioavailability of the drug to attack HCC in a more efficient manner. In the current study, we aimed to design a novel sorafenib-loaded carbon nanotubes (CNTs) formula that is able to improve the therapeutic efficacy of carried cargo against HCC and subsequently investigate the antitumour activity of this formula.Materials and methods: Sorafenib was loaded on functionalized CNTs through physical adsorption, and an alginate-based method was subsequently applied to microcapsulate the drug-loaded CNTs (CNTs-SFN). The therapeutic efficacy of the new formula was estimated and compared to that of conventional sorafenib, both in vitro (against HepG2 cells) and in vivo (in a DENA-induced HCC rat model).Results: The in vitro MTT anti-proliferative assay revealed that the drug-loaded CNTs formula was at least two-fold more cytotoxic towards HepG2 cells than was sorafenib itself. Moreover, the in vivo animal experiments proved that our innovative formula was superior to conventional sorafenib at all assessed end points. Circulating AFP-L3% was significantly decreased in the CNTs-SFN-MCs-treated group (14.0%) in comparison to that of the DENA (40.3%) and sorafenib (38.8%) groups. This superiority was further confirmed by Western blot analysis and immunofluorescence assessment of some HCC-relevant biomarkers.Conclusion: Our results firmly suggest the distinctive cancer-suppressive nature of CNTs-SFN-MCs, both against HepG2 cells in vitro and in a DENA-induced HCC rat model in vivo, with a preferential superiority over conventional sorafenib.Keywords: carbon nanotubes, sorafenib, DENA, hepatocellular carcinoma, microcapsulesElsayed MMAMostafa MEAlaaeldin ESarhan HAAShaykoon MSAllam SAhmed ARHElsadek BEMDove Medical Pressarticlecarbon nanotubessorafenibdenahepatocellular carcinomamicrocapsulesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 8445-8467 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	carbon nanotubes sorafenib dena hepatocellular carcinoma microcapsules Medicine (General) R5-920
spellingShingle	carbon nanotubes sorafenib dena hepatocellular carcinoma microcapsules Medicine (General) R5-920 Elsayed MMA Mostafa ME Alaaeldin E Sarhan HAA Shaykoon MS Allam S Ahmed ARH Elsadek BEM Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma
description	Mahmoud MA Elsayed,1 Mahmoud E Mostafa,2 Eman Alaaeldin,2,3 Hatem AA Sarhan,2 Montaser ShA Shaykoon,4 Shady Allam,5 Ahmed RH Ahmed,6 Bakheet EM Elsadek7 1Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University, Sohag, Egypt; 2Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt; 3Department of Clinical Pharmacy, Deraya University, Minia, Egypt; 4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt; 5Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt; 6Department of Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt; 7Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, EgyptCorrespondence: Bakheet EM ElsadekBiochemistry and Molecular Biology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, P. O. Box 71524, Assiut, EgyptTel +201110596270Email bakheet.elkot@azhar.edu.egPurpose: Over the past 30 years, no consistent survival benefits have been recorded for anticancer agents of advanced hepatocellular carcinoma (HCC), except for the multikinase inhibitor sorafenib (Nexavar®), which clinically achieves only &sim;3 months overall survival benefit. This modest benefit is attributed to limited aqueous solubility, slow dissolution rate and, consequently, limited absorption from the gastrointestinal tract. Thus, novel formulation modalities are in demand to improve the bioavailability of the drug to attack HCC in a more efficient manner. In the current study, we aimed to design a novel sorafenib-loaded carbon nanotubes (CNTs) formula that is able to improve the therapeutic efficacy of carried cargo against HCC and subsequently investigate the antitumour activity of this formula.Materials and methods: Sorafenib was loaded on functionalized CNTs through physical adsorption, and an alginate-based method was subsequently applied to microcapsulate the drug-loaded CNTs (CNTs-SFN). The therapeutic efficacy of the new formula was estimated and compared to that of conventional sorafenib, both in vitro (against HepG2 cells) and in vivo (in a DENA-induced HCC rat model).Results: The in vitro MTT anti-proliferative assay revealed that the drug-loaded CNTs formula was at least two-fold more cytotoxic towards HepG2 cells than was sorafenib itself. Moreover, the in vivo animal experiments proved that our innovative formula was superior to conventional sorafenib at all assessed end points. Circulating AFP-L3% was significantly decreased in the CNTs-SFN-MCs-treated group (14.0%) in comparison to that of the DENA (40.3%) and sorafenib (38.8%) groups. This superiority was further confirmed by Western blot analysis and immunofluorescence assessment of some HCC-relevant biomarkers.Conclusion: Our results firmly suggest the distinctive cancer-suppressive nature of CNTs-SFN-MCs, both against HepG2 cells in vitro and in a DENA-induced HCC rat model in vivo, with a preferential superiority over conventional sorafenib.Keywords: carbon nanotubes, sorafenib, DENA, hepatocellular carcinoma, microcapsules
format	article
author	Elsayed MMA Mostafa ME Alaaeldin E Sarhan HAA Shaykoon MS Allam S Ahmed ARH Elsadek BEM
author_facet	Elsayed MMA Mostafa ME Alaaeldin E Sarhan HAA Shaykoon MS Allam S Ahmed ARH Elsadek BEM
author_sort	Elsayed MMA
title	Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma
title_short	Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma
title_full	Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma
title_fullStr	Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma
title_full_unstemmed	Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma
title_sort	design and characterisation of novel sorafenib-loaded carbon nanotubes with distinct tumour-suppressive activity in hepatocellular carcinoma
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/3489a32513b34e969844f918bb4d15a3
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Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma

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