Preparation of hydroxy genkwanin nanosuspensions and their enhanced antitumor efficacy against breast cancer

Hydroxy genkwanin (HGK), a flavonoid compound from natural resources, showed good inhibition against the growth of breast tumor cells. However, the poor solubility restricted the further study and the in vivo drug delivery of HGK. We prepared HGK nanosuspensions by antisolvent precipitation method a...

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Main Authors: Hui Ao, Yijing Li, Haowen Li, Yian Wang, Meihua Han, Yifei Guo, Rongxing Shi, Feng Yue, Xiangtao Wang
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Drug Delivery
Subjects:
Online Access:http://dx.doi.org/10.1080/10717544.2020.1770372
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spelling doaj-d5f502701ef14f48bb9a78f91aaaf68a2021-07-06T11:30:10ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642020-01-0127181682410.1080/10717544.2020.17703721770372Preparation of hydroxy genkwanin nanosuspensions and their enhanced antitumor efficacy against breast cancerHui Ao0Yijing LiHaowen Li1Yian Wang2Meihua Han3Yifei Guo4Rongxing Shi5Feng Yue6Xiangtao Wang7Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical CollegeInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical CollegeInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical CollegeInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical CollegeInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical CollegeChina-Japan Friendship HospitalGuangdong Jiabo Pharmaceutical Co., LtdInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical CollegeHydroxy genkwanin (HGK), a flavonoid compound from natural resources, showed good inhibition against the growth of breast tumor cells. However, the poor solubility restricted the further study and the in vivo drug delivery of HGK. We prepared HGK nanosuspensions by antisolvent precipitation method and investigated their characterization, stability, hemolysis probability, release behavior in vitro, antitumor activity in vitro and in vivo, and preliminary safety through acute toxicity experiments. The resultant HGK nanosuspensions (HGK-NSps) showed an average diameter of (261.1 ± 4.8 nm), a narrow particle size distribution (PDI of 0.12 ± 0.01), spherical morphology, high drug-loading content (39.9 ± 2.3%, w/w), and good stability in various physiological media. HGK-NSps was safe for intravenous injection at low concentration and HGK was slowly released from the obtained nanosuspensions. HGK-NSps showed stronger cytotoxicity than free HGK against many tumor cells in vitro. Especially against MCF-7 cells, the IC50 value was decreased to 1.0 μg/mL, 5-fold lower than the HGK solution. In the in vivo antitumor activity study HGK-NSps (40 mg/kg) displayed a similar therapeutic effect to that of the paclitaxel injection (8 mg/kg). The preliminary acute toxicity test showed that even at the highest dose of 360 mg/kg (iv), HGK-NSps had 100% of mice survival and all the mice were in a good state, suggesting a maximum tolerated dose more than 360 mg/kg. The effective antitumor effect and good tolerance showed HGK-NSps were likely to become a safe and effective antitumor drug for the treatment of breast cancer in the future.http://dx.doi.org/10.1080/10717544.2020.1770372hydroxy genkwaninnanosuspensionscytotoxicityantitumor efficacybreast cancer
collection DOAJ
language English
format Article
sources DOAJ
author Hui Ao
Yijing Li
Haowen Li
Yian Wang
Meihua Han
Yifei Guo
Rongxing Shi
Feng Yue
Xiangtao Wang
spellingShingle Hui Ao
Yijing Li
Haowen Li
Yian Wang
Meihua Han
Yifei Guo
Rongxing Shi
Feng Yue
Xiangtao Wang
Preparation of hydroxy genkwanin nanosuspensions and their enhanced antitumor efficacy against breast cancer
Drug Delivery
hydroxy genkwanin
nanosuspensions
cytotoxicity
antitumor efficacy
breast cancer
author_facet Hui Ao
Yijing Li
Haowen Li
Yian Wang
Meihua Han
Yifei Guo
Rongxing Shi
Feng Yue
Xiangtao Wang
author_sort Hui Ao
title Preparation of hydroxy genkwanin nanosuspensions and their enhanced antitumor efficacy against breast cancer
title_short Preparation of hydroxy genkwanin nanosuspensions and their enhanced antitumor efficacy against breast cancer
title_full Preparation of hydroxy genkwanin nanosuspensions and their enhanced antitumor efficacy against breast cancer
title_fullStr Preparation of hydroxy genkwanin nanosuspensions and their enhanced antitumor efficacy against breast cancer
title_full_unstemmed Preparation of hydroxy genkwanin nanosuspensions and their enhanced antitumor efficacy against breast cancer
title_sort preparation of hydroxy genkwanin nanosuspensions and their enhanced antitumor efficacy against breast cancer
publisher Taylor & Francis Group
series Drug Delivery
issn 1071-7544
1521-0464
publishDate 2020-01-01
description Hydroxy genkwanin (HGK), a flavonoid compound from natural resources, showed good inhibition against the growth of breast tumor cells. However, the poor solubility restricted the further study and the in vivo drug delivery of HGK. We prepared HGK nanosuspensions by antisolvent precipitation method and investigated their characterization, stability, hemolysis probability, release behavior in vitro, antitumor activity in vitro and in vivo, and preliminary safety through acute toxicity experiments. The resultant HGK nanosuspensions (HGK-NSps) showed an average diameter of (261.1 ± 4.8 nm), a narrow particle size distribution (PDI of 0.12 ± 0.01), spherical morphology, high drug-loading content (39.9 ± 2.3%, w/w), and good stability in various physiological media. HGK-NSps was safe for intravenous injection at low concentration and HGK was slowly released from the obtained nanosuspensions. HGK-NSps showed stronger cytotoxicity than free HGK against many tumor cells in vitro. Especially against MCF-7 cells, the IC50 value was decreased to 1.0 μg/mL, 5-fold lower than the HGK solution. In the in vivo antitumor activity study HGK-NSps (40 mg/kg) displayed a similar therapeutic effect to that of the paclitaxel injection (8 mg/kg). The preliminary acute toxicity test showed that even at the highest dose of 360 mg/kg (iv), HGK-NSps had 100% of mice survival and all the mice were in a good state, suggesting a maximum tolerated dose more than 360 mg/kg. The effective antitumor effect and good tolerance showed HGK-NSps were likely to become a safe and effective antitumor drug for the treatment of breast cancer in the future.
topic hydroxy genkwanin
nanosuspensions
cytotoxicity
antitumor efficacy
breast cancer
url http://dx.doi.org/10.1080/10717544.2020.1770372
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