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Nanoscale Res Lett. 2019 Jul 5;14(1):223. doi: 10.1186/s11671-019-3057-0.

Bufalin-Loaded PEGylated Liposomes: Antitumor Efficacy, Acute Toxicity, and Tissue Distribution.

Author information

1
Department of Chinese Materia Medica and Natural Medicines, School of Pharmacy, Air Force Medical University, Xi'an, China.
2
Shannxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A & F University, Yangling, China.
3
Shaanxi Pharmaceutical Development Center, Xi'an, China.
4
Department of Chinese Materia Medica and Natural Medicines, School of Pharmacy, Air Force Medical University, Xi'an, China. yangqian@fmmu.edu.cn.
5
Department of Chinese Materia Medica and Natural Medicines, School of Pharmacy, Air Force Medical University, Xi'an, China. wangsiw@fmmu.edu.cn.

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.

KEYWORDS:

Acute toxicity; Antitumor efficacy; Bufalin; Liposome; Tissue distribution

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