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 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 (IC 50 ) 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 (LD 50 ) 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. Electronic supplementary material The online version of this article (10.1186/s11671-019-3057-0) contains supplementary material, which is available to authorized users.

Synthesis of glycyrrhetinic acid-modified liposomes to deliver Murrayafoline A for treatment of hepatocellular carcinoma

“…However, high concentrations of MuA-loaded GA liposomes results in decreasing thecell viability, where the concentration of 100 µM would reduce the cell viability to only 20%. This result shows the excellent performance of MuA-loaded GA liposomes, as compared to some other synthetic liposomes which is in close agreement with previous studies where the required concentrations of co-encapsulated nano-liposomes and and bufalin-loaded PEGylated Liposomes were 500 µM and 200 µM, respectively [34,35].…”

“…There are currently many methods for liver cancer therapy such as transplant, surgical resection, stereotactic body radiation therapy, and chemotherapy. However, chemotherapy with an advance of target therapy remains a synergistic treatment option [ 35 ]. Target therapy is an approach that used a molecularly targeted drug delivery systems of nanoparticles, nucleic acids, peptides, and proteins to encapsulate the small molecular drug for disease treatment [ 36 ].…”

Bufalin Induced Mitochondrial Dysfunction Promotes Apoptosis of Glioma Cells by Regulating Annexin A2 and DRP1 Proteins

“…It is reported that bufalin as one of the main active ingredients of toad venom, has a killing effect on a variety of tumor cells, and combination of bufalin with 5-urouracial can improve the drug resistance of tumor cells, reduce proliferation and induce apoptosis [17,18] . The previous studies found that bufalin and its liposome could induce apoptosis of HepG2, HCT116, A549 and U251 cells in vitro, and inhibit the growth of nude mouse xenograft gliomas in vivo [19,20] . In present study, the possible molecular mechanisms of bufalin how to inducing mitochondrial dysfunction to promote apoptosis in gliomas cells were elucidated.…”

Bufalin induces mitochondrial dysfunction and promotes apoptosis of glioma cells by regulating Annexin A2 and DRP1 protein expression

“…It has been reported that bufalin, one of the main active compounds in toad venom, has a killing effect on a variety of tumour cells, and the combination of bufalin with 5-fluorouracil can attenuate the drug resistance of tumour cells, reduce their proliferation and induce their apoptosis [ 17 , 18 ]. Previous studies showed that bufalin and related liposomes can induce the apoptosis of HepG2, HCT116, A549 and U251 cells in vitro and inhibit the growth of nude mouse xenograft gliomas in vivo [ 19 , 20 ]. In the present study, the possible molecular mechanisms by which bufalin induces mitochondrial dysfunction to promote the apoptosis of glioma cells were elucidated.…”