Drug Design Development and Therapy
·
2015
·
IF 3.028
Ran Liu,Yonglu Wang,Xueming Li,Wen Bao,Guohua Xia,Wei Chen,Jian Cheng,Yuanlong Xu,Liting Guo,Baoan Chen
To increase the encapsulation of hydrophilic antitumor agent daunorubicin (DNR) and multidrug resistance reversal agent tetrandrine (Tet) in the drug delivery system of nano-particles (NPs), a functional copolymer NP composed of poly(lactic-co-glycolic acid) (PLGA), poly-L-lysine (PLL), and polyethylene glycol (PEG) was synthesized and then loaded with DNR and Tet simultaneously to construct DNR/Tet–PLGA–PLL–PEG-NPs using a modified double-emulsion solvent evaporation/diffusion method. And to increase the targeted antitumor effect, DNR/Tet–PLGA–PLL–PEG-NPs were further modified with transferrin (Tf) due to its specific binding to Tf receptors (TfR), which is highly expressed on the surface of tumor cells. In this study, the influence of the diversity of formulation parameters was investigated systematically, such as drug loading, mean particle size, molecular weight, the concentration of PLGA–PLL–PEG–Tf, volume ratio of acetone to dichloromethane, the concentration of polyvinyl alcohol (PVA) in the external aqueous phase, the volume ratio of the internal aqueous phase to the external aqueous phase, and the type of surfactants in the internal aqueous phase. Meanwhile, its possible effect on cell viability was evaluated. Our results showed that the regular spherical DNR/Tet–PLGA–PLL–PEG–Tf-NPs with a smooth surface, a relatively low polydispersity index, and a diameter of 213.0±12.0 nm could be produced. The encapsulation efficiency was 70.23%±1.91% for DNR and 86.5%±0.70% for Tet, the moderate drug loading was 3.63%±0.15% for DNR and 4.27%±0.13% for Tet. Notably, the accumulated release of DNR and Tet could be sustained over 1 week, and the Tf content was 2.18%±0.04%. In cell viability tests, DNR/Tet–PLGA–PLL–PEG–Tf-NPs could inhibit the proliferation of K562/ADR cells in a dose-dependent manner, and the half maximal inhibitory concentration value (total drug) of DNR/Tet–PLGA–PLL–PEG–Tf-NPs was lower than that of DNR, a mixture of DNR and Tet, and DNR/Tet–PLGA–PLL–PEG-NPs. These results clearly indicate that the PLGA–PLL–PEG formulation is a potential drug delivery system for hydrophilic and hydrophobic drugs, and that Tf modification may increase its targeting properties.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Xiaoyu Cheng,Chunling Wang,Junchao Xu,Yubiao Huang,Zhuo Chen,Liyue Zhong,Chong Du,Guangjun Nie,Yinlong Zhang
Antithrombotic drugs are widely used to prevent thrombotic events in patients with cardiovascular diseases. However, they all carry varying degrees of bleeding risk. Currently, there are no approved reversal agents for antiplatelet medications, which limits their further clinical application and poses challenges in managing bleeding complications. In this proof-of-concept study, we explore the feasibility of a reversal agent system using ticagrelor and a corresponding liposome-based antidote. Specifically, we developed an azide-functionalized ticagrelor derivative (Tic-N 3 ) and a clickable DBCO-modified liposome (Lipo-DBCO) to enable controlled reversal of antiplatelet activity. Our findings demonstrate that the azide modification does not compromise the antiplatelet efficacy and biocompatibility of ticagrelor. The antiplatelet effects of Tic-N 3 were successfully reversed by Lipo-DBCO, as validated through platelet aggregation assays and in vivo mouse models of tail bleeding and liver injury. Additionally, we investigated the thiol-maleimide pairing as an alternative system, enhancing the versatility of our approach. This strategy reveals the possibility and clinical application prospects of antiplatelet drug reversal agents, offering a promising solution for the safe management of bleeding risks associated with antiplatelet therapy.
研究领域:
药理学
·
药物递送系统
·
血栓与止血
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2019
·Vol. 42
·期 24
·3611-3620
·
IF 2.516
Renxing Yi,Renjie Fu,Dapeng Li,Jin Qi,Haichun Liu
Multidrug resistance is recognized as one of the main reasons leading to the failure of chemotherapy. Studies have shown that glutathione S-transferase inhibitors could be regarded as multidrug resistance reversal agents. Herein, a method of applying enzyme immobilization, molecular docking, and high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was employed to screen glutathione S-transferase inhibitors from natural products. Magnetic mesoporous silica microspheres were synthesized and modified with a poly(dopamine) layer, which has a large quantity of amino, enabling further non-covalent binding with glutathione S-transferase. Moreover, the immobilization conditions, namely, potential of hydrogen, catalase concentration, reaction temperature and reaction time, were optimized. In total, six potential compounds were isolated and identified from Perilla frutescens (L.) Britt leaves and green tea and molecular docking was applied to identify the binding site. Rosmarinic acid, (−)-epigallocatechin-3- O -gallate and (−)-epicatechin-3-gallate showed higher binding affinity than the compounds, and their half maximal inhibitory concentration values were further determined. The results suggested that this proposed method was effective and convenient for identifying glutathione S-transferase inhibitors from natural products.
研究领域:
药物化学
·
分析化学
·
生物信息学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）