Bufalin-Loaded PEGylated Liposomes: Antitumor Efficacy, Acute Toxicity, and Tissue Distribution
Abstract Bufalin, derived from Venenum Bufonis, exerts antitumor effects but has low bioavailability and adverse effects when administered as a single agent. The purpose of this study was to evaluate the physical and chemical properties, antitumor efficacy, general pharmacology, acute toxicity, and...
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doaj-c6dcc592413b4ec0ada3947a7a4b98762020-11-25T03:11:09ZengSpringerOpenNanoscale Research Letters1931-75731556-276X2019-07-0114111010.1186/s11671-019-3057-0Bufalin-Loaded PEGylated Liposomes: Antitumor Efficacy, Acute Toxicity, and Tissue DistributionJiani Yuan0Cheng Zeng1Wei Cao2Xuanxuan Zhou3Yang Pan4Yanhua Xie5Yifang Zhang6Qian Yang7Siwang Wang8Department of Chinese Materia Medica and Natural Medicines, School of Pharmacy, Air Force Medical UniversityDepartment of Chinese Materia Medica and Natural Medicines, School of Pharmacy, Air Force Medical UniversityShannxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A & F UniversityDepartment of Chinese Materia Medica and Natural Medicines, School of Pharmacy, Air Force Medical UniversityDepartment of Chinese Materia Medica and Natural Medicines, School of Pharmacy, Air Force Medical UniversityDepartment of Chinese Materia Medica and Natural Medicines, School of Pharmacy, Air Force Medical UniversityShaanxi Pharmaceutical Development CenterDepartment of Chinese Materia Medica and Natural Medicines, School of Pharmacy, Air Force Medical UniversityDepartment of Chinese Materia Medica and Natural Medicines, School of Pharmacy, Air Force Medical UniversityAbstract Bufalin, derived from Venenum Bufonis, exerts antitumor effects but has low bioavailability and adverse effects when administered as a single agent. The purpose of this study was to evaluate the physical and chemical properties, antitumor efficacy, general pharmacology, acute toxicity, and tissue distribution profile of bufalin-loaded PEGylated liposomes (BF/PEG-LP), which were prepared in a previous study. To evaluate the safety of the preparation, a red blood cell hemolysis test was performed, which indicated that the hemolysis rate of BF/PEG-LP was significantly lower than that of bufalin alone. Cell viability assay revealed that the blank liposomes were nontoxic. In an in vitro experiment, BF/PEG-LP dose-dependently induced the apoptosis of HepG2, HCT116, A549, and U251 cancer cells, with half-maximal inhibitory concentration (IC50) values of 21.40 ± 2.39, 21.00 ± 3.34, 43.39 ± 6.43, and 31.14 ± 2.58 ng/mL, respectively, at 24 h. Tumor xenograft experiments in nude mice showed that BF/PEG-LP significantly inhibited the growth of U251 cells. Pharmacological evaluation revealed that BF/PEG-LP impacted the general behavior, independent activities, and coordination of mice after a week of administration compared with those of mice in the control group. In an acute toxicity test, the median lethal concentration (LD50) of BF and BF/PEG-LP in mice was 0.156 and 3.03 mg/kg, respectively. Tissue distribution profiles showed that the BF concentration in brain tissue was 20% higher, whereas that in heart tissue was 30% lower when BF/PEG-LP was administered to mice compared with BF. Thus, BF/PEG-LP exhibited lower hemolysis and cytotoxicity and improved pharmacokinetic and antitumor properties compared with bufalin alone, indicating its potential for future pharmacological application, particularly for glioma treatment.http://link.springer.com/article/10.1186/s11671-019-3057-0BufalinLiposomeTissue distributionAntitumor efficacyAcute toxicity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jiani Yuan Cheng Zeng Wei Cao Xuanxuan Zhou Yang Pan Yanhua Xie Yifang Zhang Qian Yang Siwang Wang |
spellingShingle |
Jiani Yuan Cheng Zeng Wei Cao Xuanxuan Zhou Yang Pan Yanhua Xie Yifang Zhang Qian Yang Siwang Wang Bufalin-Loaded PEGylated Liposomes: Antitumor Efficacy, Acute Toxicity, and Tissue Distribution Nanoscale Research Letters Bufalin Liposome Tissue distribution Antitumor efficacy Acute toxicity |
author_facet |
Jiani Yuan Cheng Zeng Wei Cao Xuanxuan Zhou Yang Pan Yanhua Xie Yifang Zhang Qian Yang Siwang Wang |
author_sort |
Jiani Yuan |
title |
Bufalin-Loaded PEGylated Liposomes: Antitumor Efficacy, Acute Toxicity, and Tissue Distribution |
title_short |
Bufalin-Loaded PEGylated Liposomes: Antitumor Efficacy, Acute Toxicity, and Tissue Distribution |
title_full |
Bufalin-Loaded PEGylated Liposomes: Antitumor Efficacy, Acute Toxicity, and Tissue Distribution |
title_fullStr |
Bufalin-Loaded PEGylated Liposomes: Antitumor Efficacy, Acute Toxicity, and Tissue Distribution |
title_full_unstemmed |
Bufalin-Loaded PEGylated Liposomes: Antitumor Efficacy, Acute Toxicity, and Tissue Distribution |
title_sort |
bufalin-loaded pegylated liposomes: antitumor efficacy, acute toxicity, and tissue distribution |
publisher |
SpringerOpen |
series |
Nanoscale Research Letters |
issn |
1931-7573 1556-276X |
publishDate |
2019-07-01 |
description |
Abstract Bufalin, derived from Venenum Bufonis, exerts antitumor effects but has low bioavailability and adverse effects when administered as a single agent. The purpose of this study was to evaluate the physical and chemical properties, antitumor efficacy, general pharmacology, acute toxicity, and tissue distribution profile of bufalin-loaded PEGylated liposomes (BF/PEG-LP), which were prepared in a previous study. To evaluate the safety of the preparation, a red blood cell hemolysis test was performed, which indicated that the hemolysis rate of BF/PEG-LP was significantly lower than that of bufalin alone. Cell viability assay revealed that the blank liposomes were nontoxic. In an in vitro experiment, BF/PEG-LP dose-dependently induced the apoptosis of HepG2, HCT116, A549, and U251 cancer cells, with half-maximal inhibitory concentration (IC50) values of 21.40 ± 2.39, 21.00 ± 3.34, 43.39 ± 6.43, and 31.14 ± 2.58 ng/mL, respectively, at 24 h. Tumor xenograft experiments in nude mice showed that BF/PEG-LP significantly inhibited the growth of U251 cells. Pharmacological evaluation revealed that BF/PEG-LP impacted the general behavior, independent activities, and coordination of mice after a week of administration compared with those of mice in the control group. In an acute toxicity test, the median lethal concentration (LD50) of BF and BF/PEG-LP in mice was 0.156 and 3.03 mg/kg, respectively. Tissue distribution profiles showed that the BF concentration in brain tissue was 20% higher, whereas that in heart tissue was 30% lower when BF/PEG-LP was administered to mice compared with BF. Thus, BF/PEG-LP exhibited lower hemolysis and cytotoxicity and improved pharmacokinetic and antitumor properties compared with bufalin alone, indicating its potential for future pharmacological application, particularly for glioma treatment. |
topic |
Bufalin Liposome Tissue distribution Antitumor efficacy Acute toxicity |
url |
http://link.springer.com/article/10.1186/s11671-019-3057-0 |
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