Optimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (MRC5) and human lung carcinoma (A549) cells

Nadiatul Atiqah Wahgiman1, Norazlinaliza Salim1,2, Mohd Basyaruddin Abdul Rahman1, Siti Efliza Ashari1,2 1Integrated Chemical BioPhysics Research, Faculty of Science, University Putra Malaysia (UPM), Serdang, Selangor 43400, Malaysia; 2Centre of Foundation Studies for Agricultural Science, Universit...

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Autores principales:	Wahgiman NA, Salim N, Abdul Rahman MB, Ashari SE
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Gemcitabine water-in-oil nanoemulsion hydrophilic drug lung cancer D-Optimal Mixture Design Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d2f3e9ab75844ef89633696e9175519f
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spelling	oai:doaj.org-article:d2f3e9ab75844ef89633696e9175519f2021-12-02T06:07:38ZOptimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (MRC5) and human lung carcinoma (A549) cells1178-2013https://doaj.org/article/d2f3e9ab75844ef89633696e9175519f2019-09-01T00:00:00Zhttps://www.dovepress.com/optimization-of-nanoemulsion-containing-gemcitabine-and-evaluation-of--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Nadiatul Atiqah Wahgiman1, Norazlinaliza Salim1,2, Mohd Basyaruddin Abdul Rahman1, Siti Efliza Ashari1,2 1Integrated Chemical BioPhysics Research, Faculty of Science, University Putra Malaysia (UPM), Serdang, Selangor 43400, Malaysia; 2Centre of Foundation Studies for Agricultural Science, University Putra Malaysia (UPM), Serdang, Selangor 43400, MalaysiaCorrespondence: Norazlinaliza SalimIntegrated Chemical BioPhysics Research, Faculty of Science, University Putra Malaysia (UPM), Serdang, Selangor 43400, MalaysiaTel +60 38 946 7807Email azlinalizas@upm.edu.myBackground: Gemcitabine (GEM) is a chemotherapeutic agent, which is known to battle cancer but challenging due to its hydrophilic nature. Nanoemulsion is water-in-oil (W/O) nanoemulsion shows potential as a carrier system in delivering gemcitabine to the cancer cell.Methods: The behaviour of GEM in MCT/surfactants/NaCl systems was studied in the ternary system at different ratios of Tween 80 and Span 80. The system with surfactant ratio 3:7 of Tween 80 and Span 80 was chosen for further study on the preparation of nanoemulsion formulation due to the highest isotropic region. Based on the selected ternary phase diagram, a composition of F1 was chosen and used for optimization by using the D-optimal mixture design. The interaction variables between medium chain triglyceride (MCT), surfactant mixture Tween 80: Span 80 (ratio 3:7), 0.9 % sodium chloride solution and gemcitabine were evaluated towards particle size as a response.Results: The results showed that NaCl solution and GEM gave more effects on particle size, polydispersity index and zeta potential of 141.57±0.05 nm, 0.168 and −37.10 mV, respectively. The optimized nanoemulsion showed good stability (no phase separation) against centrifugation test and storage at three different temperatures. The in vitro release of gemcitabine at different pH buffer solution was evaluated. The results showed the release of GEM in buffer pH 6.5 (45.19%) was higher than GEM in buffer pH 7.4 (13.62%). The cytotoxicity study showed that the optimized nanoemulsion containing GEM induced cytotoxicity towards A549 cell and at the same time reduced cytotoxicity towards MRC5 when compared to the control (GEM solution).Keywords: gemcitabine, water-in-oil nanoemulsion, hydrophilic drug, lung cancer, D-optimal mixture designWahgiman NASalim NAbdul Rahman MBAshari SEDove Medical PressarticleGemcitabinewater-in-oil nanoemulsionhydrophilic druglung cancerD-Optimal Mixture DesignMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 7323-7338 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Gemcitabine water-in-oil nanoemulsion hydrophilic drug lung cancer D-Optimal Mixture Design Medicine (General) R5-920
spellingShingle	Gemcitabine water-in-oil nanoemulsion hydrophilic drug lung cancer D-Optimal Mixture Design Medicine (General) R5-920 Wahgiman NA Salim N Abdul Rahman MB Ashari SE Optimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (MRC5) and human lung carcinoma (A549) cells
description	Nadiatul Atiqah Wahgiman1, Norazlinaliza Salim1,2, Mohd Basyaruddin Abdul Rahman1, Siti Efliza Ashari1,2 1Integrated Chemical BioPhysics Research, Faculty of Science, University Putra Malaysia (UPM), Serdang, Selangor 43400, Malaysia; 2Centre of Foundation Studies for Agricultural Science, University Putra Malaysia (UPM), Serdang, Selangor 43400, MalaysiaCorrespondence: Norazlinaliza SalimIntegrated Chemical BioPhysics Research, Faculty of Science, University Putra Malaysia (UPM), Serdang, Selangor 43400, MalaysiaTel +60 38 946 7807Email azlinalizas@upm.edu.myBackground: Gemcitabine (GEM) is a chemotherapeutic agent, which is known to battle cancer but challenging due to its hydrophilic nature. Nanoemulsion is water-in-oil (W/O) nanoemulsion shows potential as a carrier system in delivering gemcitabine to the cancer cell.Methods: The behaviour of GEM in MCT/surfactants/NaCl systems was studied in the ternary system at different ratios of Tween 80 and Span 80. The system with surfactant ratio 3:7 of Tween 80 and Span 80 was chosen for further study on the preparation of nanoemulsion formulation due to the highest isotropic region. Based on the selected ternary phase diagram, a composition of F1 was chosen and used for optimization by using the D-optimal mixture design. The interaction variables between medium chain triglyceride (MCT), surfactant mixture Tween 80: Span 80 (ratio 3:7), 0.9 % sodium chloride solution and gemcitabine were evaluated towards particle size as a response.Results: The results showed that NaCl solution and GEM gave more effects on particle size, polydispersity index and zeta potential of 141.57±0.05 nm, 0.168 and −37.10 mV, respectively. The optimized nanoemulsion showed good stability (no phase separation) against centrifugation test and storage at three different temperatures. The in vitro release of gemcitabine at different pH buffer solution was evaluated. The results showed the release of GEM in buffer pH 6.5 (45.19%) was higher than GEM in buffer pH 7.4 (13.62%). The cytotoxicity study showed that the optimized nanoemulsion containing GEM induced cytotoxicity towards A549 cell and at the same time reduced cytotoxicity towards MRC5 when compared to the control (GEM solution).Keywords: gemcitabine, water-in-oil nanoemulsion, hydrophilic drug, lung cancer, D-optimal mixture design
format	article
author	Wahgiman NA Salim N Abdul Rahman MB Ashari SE
author_facet	Wahgiman NA Salim N Abdul Rahman MB Ashari SE
author_sort	Wahgiman NA
title	Optimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (MRC5) and human lung carcinoma (A549) cells
title_short	Optimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (MRC5) and human lung carcinoma (A549) cells
title_full	Optimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (MRC5) and human lung carcinoma (A549) cells
title_fullStr	Optimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (MRC5) and human lung carcinoma (A549) cells
title_full_unstemmed	Optimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (MRC5) and human lung carcinoma (A549) cells
title_sort	optimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (mrc5) and human lung carcinoma (a549) cells
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/d2f3e9ab75844ef89633696e9175519f
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Optimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (MRC5) and human lung carcinoma (A549) cells

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