Optimization of the spherical integrity for sustained-release alginate microcarriers-encapsulated doxorubicin by the Taguchi method

Abstract This study aimed to develop biodegradable calcium alginate microcarriers with uniform particle size and spherical integrity for sustained-release targeting transarterial chemoembolization. To determine related parameters including the ratio of cross-linking volume (sodium alginate: CaCl2),...

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Autores principales: C. T. Pan, S. T. Chien, T. C. Chiang, C. K. Yen, S. Y. Wang, Z. H. Wen, C. Y. Yu, Y. L. Shiue
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Publicado: Nature Portfolio 2020
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spelling oai:doaj.org-article:1f5553f39c6642058fab2365aeba38382021-12-02T11:43:58ZOptimization of the spherical integrity for sustained-release alginate microcarriers-encapsulated doxorubicin by the Taguchi method10.1038/s41598-020-78813-12045-2322https://doaj.org/article/1f5553f39c6642058fab2365aeba38382020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78813-1https://doaj.org/toc/2045-2322Abstract This study aimed to develop biodegradable calcium alginate microcarriers with uniform particle size and spherical integrity for sustained-release targeting transarterial chemoembolization. To determine related parameters including the ratio of cross-linking volume (sodium alginate: CaCl2), concentrations of sodium alginate and CaCl2 solutions, collection distance, flow rate, stirring speed, syringe needle diameter and hardening time to fabricate the microcarriers, the Taguchi method was applied. Using different conditions, a total of 18 groups were prepared. The average size of microspheres from different groups was estimated as ~ 2 mm (range 1.1 to 1.6 mm). Signal-to-noise ratio analysis showed the optimal spherical integrity (F1) achieved when the above parameters were designed as 0.1, 2.5 wt%, 6 wt%, 8 cm, 30 mL/h, 150 rpm, 0.25 mm and 2 h, respectively. The best (F1), middle (F2) and worst (F3) groups were used for further experiments. Fourier-transform infrared spectroscopy spectrum showed that F1, F2 and F3 conformations were distinct from original sodium alginate. Drug-loaded calcium alginate microcarriers demonstrated rougher surfaces compared to microspheres without drug under transmission electron microscopy. Compared to pH 7.4, swelling rates in PBS were decreased at pH 6.5. Encapsulation and loaded efficiencies of the Dox-loaded microcarriers were estimated as ~ 40.617% and ~ 3.517%. In vitro experiments indicated that the F1 Dox-loaded microcarriers provide a well sustained-release efficacy for about two weeks at 37 °C in PBS. Treatments of calcium alginate microcarriers without the Dox in two distinct hepatocellular carcinoma-derived cell lines, Huh-7 and Hep-3B, indicated that these microcarriers were non-toxic. The Dox-loaded microcarriers displayed sustained-release capacity and reduced cell viabilities to ~ 30% in both cell lines on Day 12.C. T. PanS. T. ChienT. C. ChiangC. K. YenS. Y. WangZ. H. WenC. Y. YuY. L. ShiueNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
C. T. Pan
S. T. Chien
T. C. Chiang
C. K. Yen
S. Y. Wang
Z. H. Wen
C. Y. Yu
Y. L. Shiue
Optimization of the spherical integrity for sustained-release alginate microcarriers-encapsulated doxorubicin by the Taguchi method
description Abstract This study aimed to develop biodegradable calcium alginate microcarriers with uniform particle size and spherical integrity for sustained-release targeting transarterial chemoembolization. To determine related parameters including the ratio of cross-linking volume (sodium alginate: CaCl2), concentrations of sodium alginate and CaCl2 solutions, collection distance, flow rate, stirring speed, syringe needle diameter and hardening time to fabricate the microcarriers, the Taguchi method was applied. Using different conditions, a total of 18 groups were prepared. The average size of microspheres from different groups was estimated as ~ 2 mm (range 1.1 to 1.6 mm). Signal-to-noise ratio analysis showed the optimal spherical integrity (F1) achieved when the above parameters were designed as 0.1, 2.5 wt%, 6 wt%, 8 cm, 30 mL/h, 150 rpm, 0.25 mm and 2 h, respectively. The best (F1), middle (F2) and worst (F3) groups were used for further experiments. Fourier-transform infrared spectroscopy spectrum showed that F1, F2 and F3 conformations were distinct from original sodium alginate. Drug-loaded calcium alginate microcarriers demonstrated rougher surfaces compared to microspheres without drug under transmission electron microscopy. Compared to pH 7.4, swelling rates in PBS were decreased at pH 6.5. Encapsulation and loaded efficiencies of the Dox-loaded microcarriers were estimated as ~ 40.617% and ~ 3.517%. In vitro experiments indicated that the F1 Dox-loaded microcarriers provide a well sustained-release efficacy for about two weeks at 37 °C in PBS. Treatments of calcium alginate microcarriers without the Dox in two distinct hepatocellular carcinoma-derived cell lines, Huh-7 and Hep-3B, indicated that these microcarriers were non-toxic. The Dox-loaded microcarriers displayed sustained-release capacity and reduced cell viabilities to ~ 30% in both cell lines on Day 12.
format article
author C. T. Pan
S. T. Chien
T. C. Chiang
C. K. Yen
S. Y. Wang
Z. H. Wen
C. Y. Yu
Y. L. Shiue
author_facet C. T. Pan
S. T. Chien
T. C. Chiang
C. K. Yen
S. Y. Wang
Z. H. Wen
C. Y. Yu
Y. L. Shiue
author_sort C. T. Pan
title Optimization of the spherical integrity for sustained-release alginate microcarriers-encapsulated doxorubicin by the Taguchi method
title_short Optimization of the spherical integrity for sustained-release alginate microcarriers-encapsulated doxorubicin by the Taguchi method
title_full Optimization of the spherical integrity for sustained-release alginate microcarriers-encapsulated doxorubicin by the Taguchi method
title_fullStr Optimization of the spherical integrity for sustained-release alginate microcarriers-encapsulated doxorubicin by the Taguchi method
title_full_unstemmed Optimization of the spherical integrity for sustained-release alginate microcarriers-encapsulated doxorubicin by the Taguchi method
title_sort optimization of the spherical integrity for sustained-release alginate microcarriers-encapsulated doxorubicin by the taguchi method
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/1f5553f39c6642058fab2365aeba3838
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