Targeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer

Lei Yang,1,2 Zhenghai Zhang,1 Jian Hou,1,2 Xin Jin,1 Zhongcheng Ke,1 Dan Liu,1 Mei Du,1 Xiaobing Jia,1,2 Huixia Lv3 1Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China; 2College of Pharmacy, Jiangsu Universit...

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Autores principales:	Yang L, Zhang Z, Hou J, Jin X, Ke Z, Liu D, Du M, Jia X, Lv H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	ginsenoside compound K TPGS PEG-PCL mixed micelles antitumor non-small cell lung cancer. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ea3deabbf5834bfb9f4142f418a3c783
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spelling	oai:doaj.org-article:ea3deabbf5834bfb9f4142f418a3c7832021-12-02T02:06:52ZTargeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer1178-2013https://doaj.org/article/ea3deabbf5834bfb9f4142f418a3c7832017-10-01T00:00:00Zhttps://www.dovepress.com/targeted-delivery-of-ginsenoside-compound-k-using-tpgspeg-pcl-mixed-mi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lei Yang,1,2 Zhenghai Zhang,1 Jian Hou,1,2 Xin Jin,1 Zhongcheng Ke,1 Dan Liu,1 Mei Du,1 Xiaobing Jia,1,2 Huixia Lv3 1Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China; 2College of Pharmacy, Jiangsu University, Jiangsu, Zhenjiang, China; 3Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu Sheng, China Abstract: Ginsenoside compound K (CK) is one of the effective ingredients in antitumor composition of ginsenoside. However, the poor water solubility and significant efflux have limited the widespread clinical use of CK. In this study, preparation of novel CK-loaded D-alpha-tocopheryl polyethylene glycol 1,000 succinate/poly(ethylene glycol)-poly(ε-caprolactone) mixed micelles (CK-M) is discussed to solve the above problems. Particle size, zeta potential, and morphology were characterized using dynamic light scattering and transmission electron microscopy. CK-M are spherical shaped with an average particle size of 53.07±1.31 nm with high drug loading of 11.19%±0.87% and entrapment efficiency of 94.60%±1.45%. Water solubility of CK was improved to 3.78±0.09 mg/mL, which was ~107.35 times higher than free CK. A549 and PC-9 cells were used to evaluate in vitro cytotoxicity and cellular uptake. IC50 values of CK-M in A549 and PC-9 cells (24 h) were 25.43±2.18 and 18.35±1.90 µg/mL, respectively. Enhanced cellular uptake of CK-M was observed in both cells. Moreover, CK-M promoted tumor cell apoptosis, inhibited tumor cell invasion, metastasis, and efflux through regulation of Bax, Bcl-2, matrix metalloproteinase-2, Caspase-3, and P-glycoprotein. In vivo imaging indicated that CK-M has excellent tumor targeting effect within 24 h, and the relative tumor inhibition rate of CK-M was 52.04%±4.62% compared with control group (P<0.01). Thus, CK-M could be an appropriate delivery agent for enhanced solubility and antitumor effect of CK. Keywords: ginsenoside compound K, TPGS, PEG-PCL, mixed micelles, antitumor, non-small cell lung cancerYang LZhang ZHou JJin XKe ZLiu DDu MJia XLv HDove Medical Pressarticleginsenoside compound KTPGSPEG-PCLmixed micellesantitumornon-small cell lung cancer.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 7653-7667 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	ginsenoside compound K TPGS PEG-PCL mixed micelles antitumor non-small cell lung cancer. Medicine (General) R5-920
spellingShingle	ginsenoside compound K TPGS PEG-PCL mixed micelles antitumor non-small cell lung cancer. Medicine (General) R5-920 Yang L Zhang Z Hou J Jin X Ke Z Liu D Du M Jia X Lv H Targeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer
description	Lei Yang,1,2 Zhenghai Zhang,1 Jian Hou,1,2 Xin Jin,1 Zhongcheng Ke,1 Dan Liu,1 Mei Du,1 Xiaobing Jia,1,2 Huixia Lv3 1Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China; 2College of Pharmacy, Jiangsu University, Jiangsu, Zhenjiang, China; 3Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu Sheng, China Abstract: Ginsenoside compound K (CK) is one of the effective ingredients in antitumor composition of ginsenoside. However, the poor water solubility and significant efflux have limited the widespread clinical use of CK. In this study, preparation of novel CK-loaded D-alpha-tocopheryl polyethylene glycol 1,000 succinate/poly(ethylene glycol)-poly(ε-caprolactone) mixed micelles (CK-M) is discussed to solve the above problems. Particle size, zeta potential, and morphology were characterized using dynamic light scattering and transmission electron microscopy. CK-M are spherical shaped with an average particle size of 53.07±1.31 nm with high drug loading of 11.19%±0.87% and entrapment efficiency of 94.60%±1.45%. Water solubility of CK was improved to 3.78±0.09 mg/mL, which was ~107.35 times higher than free CK. A549 and PC-9 cells were used to evaluate in vitro cytotoxicity and cellular uptake. IC50 values of CK-M in A549 and PC-9 cells (24 h) were 25.43±2.18 and 18.35±1.90 µg/mL, respectively. Enhanced cellular uptake of CK-M was observed in both cells. Moreover, CK-M promoted tumor cell apoptosis, inhibited tumor cell invasion, metastasis, and efflux through regulation of Bax, Bcl-2, matrix metalloproteinase-2, Caspase-3, and P-glycoprotein. In vivo imaging indicated that CK-M has excellent tumor targeting effect within 24 h, and the relative tumor inhibition rate of CK-M was 52.04%±4.62% compared with control group (P<0.01). Thus, CK-M could be an appropriate delivery agent for enhanced solubility and antitumor effect of CK. Keywords: ginsenoside compound K, TPGS, PEG-PCL, mixed micelles, antitumor, non-small cell lung cancer
format	article
author	Yang L Zhang Z Hou J Jin X Ke Z Liu D Du M Jia X Lv H
author_facet	Yang L Zhang Z Hou J Jin X Ke Z Liu D Du M Jia X Lv H
author_sort	Yang L
title	Targeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer
title_short	Targeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer
title_full	Targeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer
title_fullStr	Targeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer
title_full_unstemmed	Targeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer
title_sort	targeted delivery of ginsenoside compound k using tpgs/peg-pcl mixed micelles for effective treatment of lung cancer
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/ea3deabbf5834bfb9f4142f418a3c783
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Targeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer

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