MOLECULES
·
2018
·Vol. 23
·期 3
·543
·
IF 3.098
Zhi-Feng Li,Meng-Ying Zhou,Ting Tan,Chen-Cong Zhong,Qi Wang,Shi-Lin Yang,Yu-Lin Feng,Hui Ouyang
Ziyuglycoside I (ZGS1) is a promising drug candidate for the treatment of leucopenia. Currently, information on ZGS1 and its in vivo metabolite ziyuglycoside II (ZGS2) is limited. The objective of this study was to investigate the pharmacokinetics, tissue distribution, and excretion of ziyuglycoside I (ZGS1) and its metabolite ziyuglycoside II (ZGS2) in rats. In our study, a simple and sensitive high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method was established for simultaneous determination of ZGS1 and its metabolite for Sprague-Dawley rat pharmacokinetics studies. The method was validated following internationally-approved guidelines. The results presented in this study indicated that subcutaneous administration of ZGS1 prolonged its extension time and increased the area under the curve (AUC0–t) of ZGS2 during 0 to t minutes. In summary, in this study, the pharmacokinetic characteristics of ZGS1 and its metabolite ZGS2 were defined and its tissue distribution, and excretion in rats were described. Our finding may be beneficial for leucopenia drug that focus on ZGS1.Keywords:ziyuglycoside I (ZGS1);ziyuglycoside II (ZGS2);LC-MS/MS;pharmacokinetics;tissue distribution;excretion
研究领域:
药物代谢
·
药理学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yongai Xiong,Tingting Chen,Lei Chen,Rongshan Cai
Introduction Radiotherapy and chemotherapy are the fundamental causes of myelosuppression in cancer patients, which usually induce a serious hematopoietic system toxicity, causing the hemocytes and immunity decline of patients. Ziyuglycoside I (ZgI), an active ingredient isolated from traditional Chinese medicine Sanguisorba officinalis L, has been demonstrated to increase the leucocytes and protect hematopoietic stem cells, which is related to its promotion of autophagy in hematopoietic stem cells.Methods In the present study, we formulated the SH-PEG-NH2-coated gold nanoparticles loading ZgI (ZgI-AuNPs) with a enhanced autophagy promotion in hematopoietic stem cells. ZgI-AuNPs were prepared by HAuCl4-sodium citrate reduction method, and the synthesis of ZgI-AuNPs was validated by XRD, FT-IR, DSC, and TEM findings. Furthermore, the drug loading rate and the release of ZgI were evaluated, and the ZgI-AuNPs’ effects on autophagy and immunofluorescence staining for LC3B were tested. Finally, the effect of ZgI-AuNPs on the autophagy and hematopoietic ability of HSCs in vivo was also carried out.Results The prepared ZgI-AuNPs have an irregular cubic crystal structure by TEM observation, and the average particle size was 340 ± 16.5 nm determined by DLS. The XRD, FT-IR and DSC detection showed that the ZgI had been well loaded in AuNPs, and the AuNPs can load the ZgI at a content of 160.63 ± 1.35 μg·mg−1. Meanwhile, the AuNPs can reduce the drug release rate of ZgI. Importantly, the ZgI-AuNPs enhanced autophagy of HSCs both in vitro and in vivo. At the same time, the gold nanoparticles enhance the hematopoietic effect of ZgI on mice HSCs.Conclusion Our research suggests that SH-PEG-NH2-coated gold nanoparticles loading ZgI has potential application in myelosuppression therapy.
研究领域:
纳米技术
·
药理学
·
血液学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Tingting Song,Hong Wang,Yue Liu,Rongshan Cai,Dezhi Yang,Yongai Xiong
Background Ziyuglycoside I (ZgI), an active ingredient isolated from traditional Chinese medicine Sanguisorba officinalis L, has been demonstrated to increase the leucocytes and protect hematopoietic stem cells. However, the poor solubility and a short half-life of ZgI limit its bioavailability and efficacy. The D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) has been widely used to increase the solubility, improve the encapsulation rate, and extend the half-life of drugs.Methods Here, we formulated the TPGS-modified long-circulating liposomes loading ZgI with a sustained drug release and enhanced therapy for myelosuppression. ZgI-TPGS-liposomes were manufactured using a thin-film hydration technique, followed by characterizations of physicochemical properties, including the particle size, zeta potential, TEM, SEM, FTIR, XRD, stability, drug loading (DL), encapsulation efficiency (EE). The in vitro and in vivo delivery efficiency were further evaluated by cellular uptake, in vitro drug release and in vivo pharmacokinetics. Finally, therapeutic effect on myelosuppression was investigated.Results The ZgI-TPGS-liposomes had an particle size of 97.89 ± 1.42 nm and ZP of −28.65 ± 0.16 mV. It exhibited DL of 9.06 ± 0.76% and EE of 92.34 ± 3.83%, along with excellent storage stability, cellular uptake and sustained drug release to free ZgI and liposomes without TPGS. Additionally, the TPGS modified liposomes significantly enhanced the therapeutic effect of ZgI on CTX induced myelosuppression, which can be confirmed in the apoptosis inhibition and cell viability promotion of CTX injured HSPC-1 cells. Also, the mice in vivo pharmacodynamics demonstrated that TPGS liposomes promoted ZgI increasing the numbers of leucocytes and neutrophils in myelosuppression mice induced by CTX.Conclusion Our research suggest that TPGS-modified long-circulating liposomes loading ziyuglycoside I has potential application in myelosuppression therapy.
研究领域:
药剂学
·
药理学
·
纳米技术
·
中药学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）