Development of aerosolized niosome formulation containing gemcitabine and cisplatin for in-vitro cytotoxicity against MRC5 and A549 cell lines

Gemcitabine (Gem) and cisplatin (Cis) are currently being used for lung cancer treatment has been proven to improve the life expectancy of cancer patients, but they are highly toxic in high dosages. Aerosolized niosome formulation containing a low-dosage Gem and Cis (NGC), as an alternative formulat...

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Main Author:	Mohamad Saimi, Norfatin Izzatie
Format:	Thesis
Language:	English
Published:	2020
Subjects:	Cisplatin Toxicity testing - In vitro Antibody-dependent cell cytotoxicity
Online Access:	http://psasir.upm.edu.my/id/eprint/92763/1/FS%202021%2017%20-%20IR.pdf
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spelling	my-upm-ir.927632022-04-27T02:57:35Z Development of aerosolized niosome formulation containing gemcitabine and cisplatin for in-vitro cytotoxicity against MRC5 and A549 cell lines 2020-11 Mohamad Saimi, Norfatin Izzatie Gemcitabine (Gem) and cisplatin (Cis) are currently being used for lung cancer treatment has been proven to improve the life expectancy of cancer patients, but they are highly toxic in high dosages. Aerosolized niosome formulation containing a low-dosage Gem and Cis (NGC), as an alternative formulation for lung cancer chemotherapy treatment was developed. The idea of aerosolization is to able direct delivery of a niosome formulation to the smaller airways of the lung. Niosome is a closed-bilayer vesicle in aqueous media that formed from the self-assembly of nonionic surfactant with cholesterol (Chol). NGC was prepared using a very simple heating method and was further optimized by D-optimal mixture design. The optimized NGC with 2.00 wt.% of surfactant (Tween 65 : Span 60 with ratio of 2:1), 1.01 wt.% of cholesterol and 63.06 wt.% of glycerol solution was obtained, where the other components were kept constant. The actual particle size showed good correlation with the predicted particle size with residual standard error (RSE) value less than 5%. The physicochemical characterization of optimum NGC formulation showed that the particle size, polydispersity index (PDI), and zeta potential were 166.45 nm, 0.16, and −15.28 mV, respectively. Zeta potential obtained indicates good stability against aggregation meanwhile if the zeta potential approaching zero value will lead to aggregation. The optimized NGC remained stable at 27°C with no phase separation for up to 90 days. Optimized NGC surface tension was 35.49 mN/m with an aerosol output of 96.22%, which indicates its suitability as aerosolized formulation. An in vitro drug release study using the dialysis bag diffusion technique showed controlled release for both drugs for up to 24 h penetration. The result showed that percentage of Gem release in pH 7.4 (64.71%) was 2-fold than Gem in pH 6.7 (30.38%). Meanwhile, for Cis, the percentage drug release in pH 7.4 was lower (53.55 %) than in pH 6.7 (99.58%) after 24h. This was due to the nature of drug and pH of the release medium affect the percentage of drug release. A cytotoxicity study against normal lung (MRC5) and lung cancer (A549) cell lines were performed by diluting and pipetting the formulation onto the cells. The results showed that the optimized NGC had reduced the cytotoxicity effects against both MRC5 and A549 cell lines when compared with the control (Gem + Cis alone) from very toxic (IC50 < 1.56 μg/mL) to weakly toxic (IC50 = 280.00 μg/mL) and moderately toxic (IC50 = 46.00 μg/mL), after 72 h of treatment. These results suggested that optimized NGC has the potential to be used for aerosolized chemotherapy treatment which will be promising less toxicity toward normal cell and able to inhibit cancer cell with low multidrug dosage. Cisplatin Toxicity testing - In vitro Antibody-dependent cell cytotoxicity 2020-11 Thesis http://psasir.upm.edu.my/id/eprint/92763/ http://psasir.upm.edu.my/id/eprint/92763/1/FS%202021%2017%20-%20IR.pdf text en public masters Universiti Putra Malaysia Cisplatin Toxicity testing - In vitro Antibody-dependent cell cytotoxicity Salim, Norazlinaliza
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
advisor	Salim, Norazlinaliza
topic	Cisplatin Toxicity testing - In vitro Antibody-dependent cell cytotoxicity
spellingShingle	Cisplatin Toxicity testing - In vitro Antibody-dependent cell cytotoxicity Mohamad Saimi, Norfatin Izzatie Development of aerosolized niosome formulation containing gemcitabine and cisplatin for in-vitro cytotoxicity against MRC5 and A549 cell lines
description	Gemcitabine (Gem) and cisplatin (Cis) are currently being used for lung cancer treatment has been proven to improve the life expectancy of cancer patients, but they are highly toxic in high dosages. Aerosolized niosome formulation containing a low-dosage Gem and Cis (NGC), as an alternative formulation for lung cancer chemotherapy treatment was developed. The idea of aerosolization is to able direct delivery of a niosome formulation to the smaller airways of the lung. Niosome is a closed-bilayer vesicle in aqueous media that formed from the self-assembly of nonionic surfactant with cholesterol (Chol). NGC was prepared using a very simple heating method and was further optimized by D-optimal mixture design. The optimized NGC with 2.00 wt.% of surfactant (Tween 65 : Span 60 with ratio of 2:1), 1.01 wt.% of cholesterol and 63.06 wt.% of glycerol solution was obtained, where the other components were kept constant. The actual particle size showed good correlation with the predicted particle size with residual standard error (RSE) value less than 5%. The physicochemical characterization of optimum NGC formulation showed that the particle size, polydispersity index (PDI), and zeta potential were 166.45 nm, 0.16, and −15.28 mV, respectively. Zeta potential obtained indicates good stability against aggregation meanwhile if the zeta potential approaching zero value will lead to aggregation. The optimized NGC remained stable at 27°C with no phase separation for up to 90 days. Optimized NGC surface tension was 35.49 mN/m with an aerosol output of 96.22%, which indicates its suitability as aerosolized formulation. An in vitro drug release study using the dialysis bag diffusion technique showed controlled release for both drugs for up to 24 h penetration. The result showed that percentage of Gem release in pH 7.4 (64.71%) was 2-fold than Gem in pH 6.7 (30.38%). Meanwhile, for Cis, the percentage drug release in pH 7.4 was lower (53.55 %) than in pH 6.7 (99.58%) after 24h. This was due to the nature of drug and pH of the release medium affect the percentage of drug release. A cytotoxicity study against normal lung (MRC5) and lung cancer (A549) cell lines were performed by diluting and pipetting the formulation onto the cells. The results showed that the optimized NGC had reduced the cytotoxicity effects against both MRC5 and A549 cell lines when compared with the control (Gem + Cis alone) from very toxic (IC50 < 1.56 μg/mL) to weakly toxic (IC50 = 280.00 μg/mL) and moderately toxic (IC50 = 46.00 μg/mL), after 72 h of treatment. These results suggested that optimized NGC has the potential to be used for aerosolized chemotherapy treatment which will be promising less toxicity toward normal cell and able to inhibit cancer cell with low multidrug dosage.
format	Thesis
qualification_level	Master's degree
author	Mohamad Saimi, Norfatin Izzatie
author_facet	Mohamad Saimi, Norfatin Izzatie
author_sort	Mohamad Saimi, Norfatin Izzatie
title	Development of aerosolized niosome formulation containing gemcitabine and cisplatin for in-vitro cytotoxicity against MRC5 and A549 cell lines
title_short	Development of aerosolized niosome formulation containing gemcitabine and cisplatin for in-vitro cytotoxicity against MRC5 and A549 cell lines
title_full	Development of aerosolized niosome formulation containing gemcitabine and cisplatin for in-vitro cytotoxicity against MRC5 and A549 cell lines
title_fullStr	Development of aerosolized niosome formulation containing gemcitabine and cisplatin for in-vitro cytotoxicity against MRC5 and A549 cell lines
title_full_unstemmed	Development of aerosolized niosome formulation containing gemcitabine and cisplatin for in-vitro cytotoxicity against MRC5 and A549 cell lines
title_sort	development of aerosolized niosome formulation containing gemcitabine and cisplatin for in-vitro cytotoxicity against mrc5 and a549 cell lines
granting_institution	Universiti Putra Malaysia
publishDate	2020
url	http://psasir.upm.edu.my/id/eprint/92763/1/FS%202021%2017%20-%20IR.pdf
_version_	1747813761381564416

Development of aerosolized niosome formulation containing gemcitabine and cisplatin for in-vitro cytotoxicity against MRC5 and A549 cell lines

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