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34篇 您的检索式:作者名="Liu Zhonggui"
    题名 作者 年代 出处 被引量
1Redox-sensitive prodrug nanoassemblies based on linoleic acid-modified docetaxel to resist breast cancers显示文摘Prodrug nanoassemblies, which can refrain from large excipients, achieve higher drug loading and control drug release, have been placed as the priority in drug delivery system. Reasoning that glutathione(GSH) and reactive oxygen species(ROS) are highly upgraded in tumor tissues which makes them attractive targets for drug delivery system, we designed and synthetized a novel prodrug which utilized mono thioether bond as a linker to bridge linoleic acid(LA) and docetaxel(DTX). This mono thioether-linked conjugates(DTX-S-LA) could self-assemble into nanoparticles without the aid of much excipients. The mono thioether endowed the nanoparticles redox sensitivity resulting in specific release at the tumor tissue. Our studies demonstrated that the nanoassemblies had uniform particle size, high stability and fast release behavior. DTX-S-LA nanoassemblies outperformed DTX solution in pharmacokinetic profiles for it had longer circulation time and higher area under curve(AUC). Compared with DTX solution, the redox dual-responsive nanoassemblies had comparable cytotoxic activity. Besides, the antitumor efficacy was evaluated in mice bearing 4 T1 xenograft. It turned out this nanoassemblies couldenhance anticancer efficacy by increasing the dose because of higher tolerance. Overall, these results indicated that the redox sensitivity nanoassemblies may have a great potential to cancer therapy.Meng Li Liwen Zhao Tao Zhang Yue Shu Zhonggui He Yan Ma Dan Liu Yongjun Wang 2019Acta Pharmaceutica Sinica B2019,9,2:10
2Transformative hyaluronic acid-based active targeting supramolecular nanoplatform improves long circulation and enhances cellular uptake in cancer therapy显示文摘Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overexpressing in the reticuloendothelial system(RES). Therefore,polyethylene glycol(PEG) modification of HA-based DDS is necessary to reduce RES capture.Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement,significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform(Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage.The in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a 'stealth' state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a 'recognition' state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution.Lu Zhong Lu Xu Yanying Liu Qingsong Li Dongyang Zhao Zhenbao Li Huicong Zhang Haotian Zhang Qiming Kan Yongjun Wang Jin Sun Zhonggui He 2019Acta Pharmaceutica Sinica B2019,9,2:7
3Ratiometric delivery of doxorubicin and berberine by liposome enables superior therapeutic index than Doxil?显示文摘Although the appearance of Doxil alleviated the cardiotoxicity of DOX, the progression-free survival of patients was not prolonged compared with traditional medication regimens, and side effects such as hand-foot syndrome has occurred. In order to solve this dilemma, we have designed a novel co-delivery strategy to construct a co-loaded liposome of berberine(BER) and doxorubicin(DOX), which was called Lipo Be Do. The optimal synergistic ratio of the two drugs was screened by cell cytotoxicity experiments in vitro, and the optimal attenuation ratio was further determined by in vivo cardiac H&E staining pathological sections. The optimal combination treatment caused a robust increase in apoptotic cells of 4T1, as compared to drug alone treatment. The prepared co-loaded liposome, Lipo Be Do, had high encapsulation efficiency and good stability. The nanoliposome carrier controlled the biological fate of the drugs and maintained a pre-defined optimal ratio in vivo. The Lipo Be Do significantly inhibited tumor growth in 4T1 murine mammary carcinoma model compared with Doxil(P < 0.05), and completely overcame the myocardial rupture toxicity caused by Doxil in mice. Our co-loaded liposome delivery platform technology provided a new direction for the clinical treatment of triple-negative breast cancer and the safe application of DOX.Ruoshi Zhang Yingxi Zhang Yue Zhang Xin Wang Xuanming Gao Yuyan Liu Xuanbo Zhang Zhonggui He Dun Wang Yongjun Wang 2020Asian Journal of Pharmaceutical Sciences2020,15,3:4
4Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies显示文摘Homodimeric prodrug-based self-assembled nanoparticles,with carrier-free structure and ultrahigh drug loading,is drawing more and more attentions.Homodimeric prodrugs are composed of two drug molecules and a pivotal linkage.The influence of the linkages on the self-assembly,in vivo fate and antitumor activity of homodimeric prodrugs is the focus of research.Herein,three docetaxel(DTX)homodimeric prodrugs are developed using different lengths of diselenide bond-containing linkages.Interestingly,compared with the other two linkages,the longest diselenide bond-containing linkage could facilitate the self-delivery of DTX prodrugs,thus improving the stability,circulation time and tumor targeting of prodrug nanoassemblies.Besides,the extension of linkages reduces the redox-triggered drug release and cytotoxicity of prodrug nanoassemblies in tumor cells.Although the longest diselenide bond-containing prodrug nanoassemblies possessed the lowest cytotoxicity to 4T1 cells,their stable nanostructure maintained intact during circulation and achieve the maximum accumulation of DTX in tumor cells,which finally“turned the table”.Our study illustrates the crucial role of linkages in homodimeric prodrugs,and gives valuable proposal for the development of advanced nano-DDS for cancer treatment.Lingxiao Li Shiyi Zuo Fudan Dong Tian Liu Yanlin Gao Yinxian Yang Xin Wang Jin Sun Bingjun Sun Zhonggui He 2021Asian Journal of Pharmaceutical Sciences2021,16,3:3
5Co-amorphous solid dispersion systems of lacidipine-spironolactone with improved dissolution rate and enhanced physical stability显示文摘Co-amorphous solid dispersion(C-ASD)systems have attracted great attention to improve the solubility of poorly soluble drugs,but the selection of an appropriate stabilizer to stabilize amorphous forms is still a huge challenge.Herein,C-ASD system of two clinical combined used drugs(lacidipine(LCDP)and spironolactone(SPL))as stabilizers to each other,was prepared by solvent evaporation method.The effects of variation in molar ratio of LCDP and SPL(3:1,1:1,1:3,1:6,and 1:9)on the drug release characteristics were explored.Polarized light microscopy(PLM),powder X-ray diffraction(PXRD),differential scanning calorimetry(DSC)and thermogravimetric analysis(TGA)were employed to evaluate the solid states.Prepared C-ASDs were further studied for their stability under the high humidity(RH 92.5%).Further analysis of C-ASDs via Fourier-transform infrared spectroscopy(FTIR)and Raman spectroscopy confirmed that hydrogen bond interactions between the two drugs played a significant role in maintaining the stability of the C-ASDs systems.Moreover,molecular dynamic(MD)simulations provided a clear insight into the stability mechanism at the molecular level.This study demonstrated the novel drug-drug C-ASDs systems is a promising formulation strategy for improved dissolution rate and enhanced physical stability of poorly soluble drugs.Zhaomeng Wang Mengchi Sun Tian Liu Zisen Gao Qing Ye Xiao Tan Yanxian Hou Jin Sun Dun Wang Zhonggui He 2019Asian Journal of Pharmaceutical Sciences2019,14,1:2
6Emerging systemic delivery strategies of oncolytic viruses:A key step toward cancer immunotherapy显示文摘Oncolytic virotherapy(OVT)is a novel type of immunotherapy that induces anti-tumor responses through selective self-replication within cancer cells and oncolytic virus(OV)-mediated immunostimulation.Notably,talimogene laherparepvec(T-Vec)developed by the Amgen company in 2015,is the first FDA-approved OV product to be administered via intratumoral injection and has been the most successful OVT treatment.However,the systemic administration of OVs still faces huge challenges,including in vivo pre-existing neutralizing antibodies and poor targeting delivery efficacy.Recently,state-of-the-art progress has been made in the development of systemic delivery of OVs,which demonstrates a promising step toward broadening the scope of cancer immunotherapy and improving the clinical efficacy of OV delivery.Herein,this review describes the general characteristics of OVs,focusing on the action mechanisms of OVs as well as the advantages and disadvantages of OVT.The emerging multiple systemic administration approaches of OVs are summarized in the past five years.In addition,the combination treatments between OVT and traditional therapies(chemotherapy,thermotherapy,immunotherapy,and radiotherapy,etc.)are highlighted.Last but not least,the future prospects and challenges of OVT are also discussed,with the aim of facilitating medical researchers to extensively apply the OVT in the cancer therapy.Weiyue Ban Jianhuan Guan Hanwei Huang Zhonggui He Mengchi Sun Funan Liu Jin Sun 2022Nano Research2022,15,5:2
7Development and validation of a UPLC–MS/MS assay for the determination of gemcitabine and its L-carnitine ester derivative in rat plasma and its application in oral pharmacokinetics显示文摘A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative(2’-deoxy-2’, 2’-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine, JDR) in rat plasma was developed and validated.The conventional plasma sample preparation method of nucleoside analogues is solidphase extraction(SPE) which is time-consuming and cost-expensive. In this study, gradient elution with small particles size solid phase was applied to effectively separate gemcitabine and JDR, and protein precipitation pretreatment was adopted to remove plasma protein and extract the analytes with high recovery(>81%). Method validation was performed as per the FDA guidelines, and the standard curves were found to be linear in the range of 5–4000 ng/ml for JDR and 4–4000 ng/ml for gemcitabine, respectively. The lower limit of quantitation(LLOQ)of gemcitabine and JDR was 4 and 5 ng/ml, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Finally, the developed method was successfully applied to investigate the pharmacokinetic studies of JDR and gemcitabine after oral administration to rats.Gang Wang Dongyang Zhao Hongxiang Chen Dawei Ding Longfa Kou Lifang Sun Chenxia Hao Xincong Li Kai Jia Qiming Kan Xiaohong Liu Zhonggui He Jin Sun 2017Asian Journal of Pharmaceutical Sciences2017,12,5:2
8Naringenin nanocrystals for improving antirheumatoid arthritis activity显示文摘Naringenin(NAR)is recognized for its anti-inflammatory activity.However,the clinical application of NAR is limited by low bioavailability,which is attributed to its poor aqueous solubility.In this study,we aimed to improve the therapeutic efficacy of NAR by formulating it into nanocrystals(NCs)via wet milling.The obtained NARNCs exhibited superior dissolution behaviors,increased cellular uptake,and enhanced transcellular diffusion relative to those of bulk NAR.Oral administration of NARNCs also significantly improved bioavailability in rats.In addition,the NARNCs effectively improved rheumatoid arthritis treatment in collagen-induced arthritic rats by reducing inflammatory cell infiltration and synovial damage.These results indicate that NARNCs provides a promising strategy for rheumatoid arthritis treatment.Guangshuai Zhang Guangyuan Sun Haishan Guan Mo Li Yanhua Liu Baocheng Tian Zhonggui He Qiang Fu 2021Asian Journal of Pharmaceutical Sciences2021,16,6:1
9Dense small cell clustering based on undirected weighted graph for local mobility management显示文摘The concept of dense small cell has been recently emerged as a promising architecture that can significantly improve spectrum efficiency and system capacity.However, it brings frequent handover for user equipment(UE).Furthermore, this will bring a great deal of signaling overhead to the core network.Virtual technology has been received widespread attention for solving this problem.Its essence is to form virtual cells by clustering various terminals properly.The local mobility management proposed recently is based on the virtual technology.Therefore, the formation process of virtual cells is the basis for the research in local mobility management.So clustering scheme for dense small cell network has been studied in this paper, and a maximum benefit merging algorithm based on undirected weighted graph has been proposed.There are X2 interfaces between the cluster head and each of cluster members within the same cluster.The cluster heads manage the handover among cluster members acting as the local anchors.The proposed clustering scheme is useful for local mobility management.The simulation results show that the proposed clustering algorithm can decrease the signaling overhead more than 70% and 20% compared with the non-clustering algorithm and other clustering algorithms respectively.Li Yingying Ma Zhonggui Liu Liyu Yan Wenbo 2016The Journal of China Universities of Posts and Telecommunications2016,23,5:1
10Study on degradation kinetics of epalrestat in aqueous solutions and characterization of its major degradation products under stress degradation conditions by UHPLC-PDA-MS/MS显示文摘Drug stability is closely related to drug safety and needs to be considered in the process of drug production,package and storage.To investigate the stability of epalrestat,a carboxylic acid derivative,a reversed-phase high-performance liquid chromatography(RP-HPLC)method was developed in this study and applied to analyzing the degradation kinetics of epalrestat in aqueous solutions in various conditions,such as different pH,temperatures,ionic strengths,oxidation and irradiation.The calibration curve was A=1.6×10^5C–1.3×10^3(r=0.999)with the liner range of 0.5–24μg/mL,the intra-day and inter-day precision was less than 2.0%,as was the repeatibility.The average accuracy for different concentrations was more than 98.5%,indicating that perfect recoveries were achieved.Degradation kinetic parameters such as degradation rate constants(k),activation energy(Ea)and shelf life(t0.9)under different conditions were calculated and discussed.The results indicated that the degradation behavior of epalrestat was pH-dependent and the stability of epalrestat decreased with the rised irradiation and ionic strength;however,it was more stable in neutral and alkaline conditions as well as lower temperatures.The results showed that the degradation kinetics of epalrestat followed first-order reaction kinetics.Furthermore,the degradation products of epalrestat under stress conditions were identified by UHPLC-PDA-MS/MS,with seven degradation products being detected and four of them being tentatively identified.Hong Sun Suyan Liu Xun Gao Zhili Xiong Zhonggui He Longshan Zhao 2019Journal of Pharmaceutical Analysis2019,9,6:1
11Easy Mesh Cutting显示文摘Ji Zhongping Liu Ligang Chen Zhonggui 2006Computer Graphics Forum2006,25,3:1
12Minor change in the length of carbon chain has a great influence on the antitumor effect of paclitaxel-fatty alcohol prodrug nanoassemblies:Small roles,big impacts显示文摘Prodrug-based nanoassembly emerges as a hopeful way for the efficient delivery of antitumor drugs,with carrier-free structure and ultra-high drug loading.Carbon chains are widely used to design self-assembling prodrugs.The impacts of the length of carbon chains on the self-assembly stability,drug delivery efficiency and antitumor effect of prodrugs have not been fully elucidated.Here,three paclitaxel prodrugs were synthesized by conjugating paclitaxel with octanol(C_(8)),decanol(C_(10))or dodecanol(C_(12))through disulfide bond.The three prodrugs could form homogeneous nanoparticles,with over 50%drug loading and redox dual-responsivity.Interestingly,the length extension of carbon chains ameliorates the self-assembly and the colloidal stability of prodrugs,thus improving the drug delivery efficiency.The optimal paclitaxel-dodecanol prodrug nanoassemblies exhibit better antitumor efficacy than Taxol and Abraxane.These findings are meaningful for the rational design of advanced nanomedicines in cancer therapy.Xin Wang Lingxiao Li Danping Wang Shiyi Zuo Tian Liu Fudan Dong Xuanbo Zhang Zhonggui He Bingjun Sun Jin Sun 2022Nano Research2022,15,4:1
13Prediction of Human Drug Absorption Using Liposome Electrokinetic Chromatography显示文摘Yongjun Wang Jin Sun Hongzhuo Liu Yanjiao Wang Zhonggui He 2007Chromatographia (-)2007,,3:1
14Exploring the relationship of hyaluronic acid molecular weight and active targeting efficiency for designing hyaluronic acid-modified nanoparticles显示文摘Although it is reported that the targeting ability of hyaluronic acid(HA)-based nanoparticles(NPs) is molecular weight(MW) dependent,the influence of HA MW on targeting efficiency of HA-functionalized NPs and the underlying mechanism remain elusive. In this study,we constituted three HA-functionalized Dox-loaded NPs(Dox/HCVs) different HA MWs(7,63,and 102 k Da) and attempted to illustrate the effects of HA MW on the targeting efficiency.The three Dox/HCVs had similar physiochemical and pharmaceutical characteristics,but showed different affinity to CD44 receptor. Furthermore,Dox/HCV-63 exerted the best targeting effect and the highest cytotoxicity compared with Dox/HCV-7 and Dox/HCV-102. It was interesting to found that both the HA-CD44 binding affinity and induced CD44 clustering by HA-based NPs were HA MW-dependent,the two of which determine the apparent targeting efficacy of Dox/HCV NPs in the conflicting directions. Those results laid a good foundation for rationally designing HA-based NPs in cancer therapy.Lu Zhong Yanying Liu Lu Xu Qingsong Li Dongyang Zhao Zhenbao Li Huicong Zhang Haotian Zhang Qiming Kan Jin Sun Zhonggui He 2019Asian Journal of Pharmaceutical Sciences2019,14,5:1
15Impact of the amount of PEG on prodrug nanoassemblies for efficient cancer therapy显示文摘PEGylation has been widely used to improve the pharmacokinetic properties of prodrug self-assembled nanoparticles(prodrug-SANPs).However,the impacts of the amount of PEG on the self-assemble stability,cellular uptake,pharmacokinetics,and antitumor efficacy of prodrug-SANPs are still unknown.Herein,selenoether bond bridged docetaxel dimeric prodrug was synthesized as the model prodrug.Five prodrug-SANPs were designed by using different mass ratios of prodrugs to PEG(W_(prodrug)/W_(DSPE-mPEG2000)=10:0,9:1,8:2,7:3 and 6:4),and defined as Pure drug NPs,9:1NPs,8:2NPs,7:3 NPs and 6:4 NPs,respectively.Interestingly,8:2 NPs formed the most compact nanostructure,thus improving the self-assemble stability and pharmacokinetics behavior.In addition,the difference of these prodrug-SANPs in cellular uptake was investigated,and the influence of PEG on cytotoxicity and antitumor efficacy was also clarified in details.The 8:2 NPs exhibited much better antitumor efficacy than other prodrug-SANPs and even commercial product.Our findings demonstrated the pivotal role of the amount of PEG on prodrug-SANPs.Yaqiao Li Lingxiao Li Qianhui Jin Tian Liu Jin Sun Yongjun Wang Zhijun Yang Zhonggui He Bingjun Sun 2022Asian Journal of Pharmaceutical Sciences2022,17,2:1
16Preparation and Characterization of a Submicron Lipid Emulsion of Docetaxel: Submicron Lipid Emulsion of Docetaxel显示文摘Kun Gao Jin Sun Kai Liu Xiaohong Liu Zhonggui He 2008Drug Development and Industrial Pharmacy2008,,11:1
17Folate and CD 44 Receptors Dual‐Targeting Hydrophobized Hyaluronic Acid Paclitaxel‐Loaded Polymeric Micelles for Overcoming Multidrug Resistance and Improving Tumor Distribution显示文摘Yanhua Liu Jin Sun He Lian Wen Cao Yongjun Wang Zhonggui He 2014J Pharm Sci2014,,5:1
18Structurally defined tandem-responsive nanoassemblies composed of dipeptide-based photosensitive derivatives and hypoxia-activated camptothecin prodrugs against primary and metastatic breast tumors显示文摘Substantial progress in the use of chemo-photodynamic nano-drug delivery systems(nanoDDS) for the treatment of the malignant breast cancer has been achieved. The inability to customize precise nanostructures, however, has limited the therapeutic efficacy of the prepared nano-DDS to date. Here,we report a structurally defined tandem-responsive chemo-photosensitive co-nanoassembly to eliminate primary breast tumor and prevent lung metastasis. This both-in-one co-nanoassembly is prepared by assembling a biocompatible photosensitive derivative(pheophorbide-diphenylalanine peptide, PPADA) with a hypoxia-activated camptothecin(CPT) prodrug [(4-nitrophenyl) formate camptothecin, NCPT]. According to computational simulations, the co-assembly nanostructure is not the classical core-shell type, but consists of many small microphase regions. Upon exposure to a 660 nm laser,PPA-DA induce high levels of ROS production to effectively achieve the apoptosis of normoxic cancer cells. Subsequently, the hypoxia-activated N-CPT and CPT spatially penetrate deep into the hypoxic region of the tumor and suppress hypoxia-induced tumor metastasis. Benefiting from the rational design of the chemo-photodynamic both-in-one nano-DDS, these nanomedicines exhibit a promising potential in the inhibition of difficult-to-treat breast tumor metastasis in patients with breast cancer.Mengchi Sun Hailun Jiang Tian Liu Xiao Tan Qikun Jiang Bingjun Sun Yulong Zheng Gang Wang Yang Wang Maosheng Cheng Zhonggui He Jin Sun 2022Acta Pharmaceutica Sinica B2022,12,2:1
19Folate and CD44 Receptors Dual-Targeting Hydrophobized Hyaluronic Acid Paclitaxel-Loaded Polymeric Micelles for Overcoming Multidrug Resistance and Improving Tumor Distribution显示文摘Yanhua Liu Jin Sun He Lian Wen Cao Yongjun Wang Zhonggui He 2014Journal of Pharmaceutical Sciences2014,,5:1
20In vitro/vivo assessment of praziquantel nanocrystals: Formulation, characterization, and pharmacokinetics in beagle dogs显示文摘To investigate the impact of particle size on in vitro/vivo performance of praziquantel(PZQ), nanocrystals(NCs) and microcrystals(MCs) of PZQ were prepared using the methods of wet milling and jet milling, respectively. PZQ NCs and MCs were characterized with dynamic light scattering, laser particle size analyzer, transmission electron microscopy, differential scanning calorimetry, X-ray powder diffraction and fourier transform infrared spectroscopy. The average diameters of PZQ NCs and MCs were 364.4 nm and 3.7 μm, respectively. No change in crystalline form was observed. Dissolution tests were performed in two different media, where the cumulative dissolution and dissolution rate of NCs were significantly improved in comparison with those of MCs and KANGQING~? in non-sink condition. Similarly, oral bioavailability of PZQ NCs in beagle dogs was 1.68( P < 0.05) and 1.83 fold( P < 0.01) higher than that of MCs and KANGQING~? . Considering the advantages of in vitro/vivo performance and facile preparation, PZQ NCs may have a great application in the treatment of schistosomiasis.Ruyi Yang Tao Zhang Jiang Yu Yan Liu Yingli Wang Zhonggui He 2019Asian Journal of Pharmaceutical Sciences2019,14,3:1
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