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检索条件"任意字段=2014年中国药物制剂大会——中国药学会药剂专业委员会年会、第六届亚洲阿登制药技术研讨会暨国际控释协会中国分会年会"

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Reversion of multidrug resistance by coadministration of doxorubicin and bromotetrandrine in polymer-lipid hybrid nanoparticles

Reversion of multidrug resistance by coadministration of dox...

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2014中国药物制剂大会——中国药学会药剂专业委员会年会、第六届亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Xi Cao Ting Zhang Tao Gong Zhi-Rong Zhang Yao Fu Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan University

Female breast cancer is one of the most common cancers among middle aged and older *** to NCI statistics,there will be 232,670 new cases and 40,000 people will die of this disease in *** has been proven the most effective treatment for breast ***,the multidrug resistance(MDR) remains the major obstacle to chemotherapeutic success,leading to low therapeutic *** MDR effect appeared to result in decreased drug influx,increased drug efflux,DNA repair activation,detoxification and inactivation of apoptosis pathways with simultaneous activation of anti-apoptotic cellular defense *** overexpression of drug efflux transporters on the tumor cells such as the P-glycoprotein(P-gp) were reported to be associated with chemoresistence.P-gp is a 170-kDa membrane-associated glycoprotein,which can reduce the effective cellular concentration of structurally diverse substrates by activating drug *** this study,a lipid-nanoparticle based delivery system was developed for the coadministration of a chemotherapeutic agent,doxorubicin,and a specific P-gp inhibitor(W198).Specifically,nanoparticles were prepared by a simple lipid film hydration-high pressure homogenization *** obtained nanoparticles displayed near spherical shapes with an average diameter of about 100 nm and an over 80%of encapsulation *** cellular uptake behavior of nanoparticles were evaluated in human breast cancer MCF-7 cells and its multidrug resistant counterpart MCF-7/ADR *** indicated W198 significantly increased the influx of DOX into the MCF-7/ADR cells.

关键词： multidrug resistance P-glycoprotein inhibitor doxorubicin bromotetrandrine nanoparticles

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The anti-tumor activity of conjugated linoleic acid-paclitaxel(CLA-PTX)

The anti-tumor activity of conjugated linoleic acid-paclitax...

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2014中国药物制剂大会——中国药学会药剂专业委员会年会、第六届亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者：张烜北京大学药学院药剂学系

Considering the effects of conjugated linoleic acid(CLA) on anti-tumor and synergistic anti-tumor activity with taxane,we synthesized a novel paclitaxel(PTX)conjugate,*** anti-tumor activity of CLA-PTX was evaluated in vitro and in *** results indicated that CLA-PTX was stable in PBS and rat plasma in vitro and had slight effect of arresting cell cycle progressbn at the G2-M *** conjugate showed higher cellular uptake efficiency on C6 glioma *** entire pharmacokinetic index revealed the significant enhancement of the conjugate pharmacokinetics compared with that in ***-PTX,unlike PTX,could distribute in brain tissue and retained higher *** anti-tumor efficacy in brain tumor-bearing rats after administering CLA-PTX was significantly higher than that after giving TaxoL In order to enhance the safety of CLA-PTX solution,a novel CLA-PTX microemulsion was *** results indicated that CLA-PTX microemulsion is a novel formulation with significant antitumor efficacy in the treatment of brain tumors,and is safer than CLA-PTX solutioa The antitumor efficacy of CLA-PTX on B16-F10 melanoma cell line was also investigated in vitro and in *** study demonstrated that CLA-PTX has significant antitumor activity in B16-F10 cell *** targeted delivery system of CLA-PTX was also *** prepared a novel delivery system of iRGD-modified liposomes containing CLA-PTX(iRGD-SSL-CLA-PTX).The antitumor activity of iRGD-SSL-CLA-PTX was confirmed on B16-F10 melanoma in vitro and in vivo,which was higher than that of CLA-PTX solution and CLA-PTX liposomes.

关键词： PTX CLA-PTX The anti-tumor activity of conjugated linoleic acid-paclitaxel

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A Novel Collaborative Assembly Strategy for Tumor-Targeted siRNA Delivery

A Novel Collaborative Assembly Strategy for Tumor-Targeted s...

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2014中国药物制剂大会——中国药学会药剂专业委员会年会、第六届亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Qiong Sun Ran Mo Yunkai Shang 张灿 Center of Drug Discovery and Department of Pharmaceutics China Pharmaceutical University 中国药科大学新药研究中心

Development of safe and efficient small interfering RNA（siRNA） delivery systems still remains elusive in clinical applications of siRNA for cancer treatment.[1]An ideal siRNA delivery system is required to be stable in the blood for preferential tumor targeting and overcome a variety of physiological barriers followed by efficient intracellular siRNA release for enhanced therapeutic efficacy. As the most common non-viral vectors used for siRNA delivery,cationic lipids and polymers can efficiently complex siRNA via electrostatic ***,such complex with a cationic surface charge often suffers from poor serum stability,complement activation,inflammatory response,thereby yielding severe toxicities after systematic administration Although polyanions,the polymers bearing repeating anionic units,have been applied to shield the positive charge of the complex by encapsulation,the incorporated polyanions inevitably disturb the electrostatic interaction between cationic constituents and anionic siRNA by competitive binding to the complex,which results in the leakage of preloaded ***,the surface polyanions are inclined to be displaced by negatively charged blood proteins,which leads to an unexpected release of siRNA during the circulation.[4]Herein,we report a novel "collaborative assembly" strategy for an optimal tumor-targeted siRNA delivery,denoted as RSC-HA,a click chemistry-mediated hyaluronic acid（HA）-conjugated redox-sensitive complex with *** collaboratively-assembled RSC-HA was constructed by "electrostatic assembly" of a redox-responsive cationic liposome with siRNA,which was further constructed by HA based on "chemical assembly".As control,only electrostatically-assembled RSC/HA was also engineered by coating the HA on the surface of *** was confirmed that RSC-HA showed an enhanced colloidal stability in physiological conditions compared with RSC/***,this original assembly strategy has the universal significance and im

关键词： A Novel Collaborative Assembly Strategy for Tumor-Targeted siRNA Delivery siRNA

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Synthesis,Characterization and Anticancer Activity of Pluronic F68-Curcumin Conjugate Micelles

Synthesis,Characterization and Anticancer Activity of Pluron...

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2014中国药物制剂大会——中国药学会药剂专业委员会年会、第六届亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： YueeCai Xiaobin Fang Jinming Zhang Yunyun Zhu Yitao Wang Meiwan Chen State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of Macau

Curcumin(CUR),a nontoxic polyphenol derived from the rhizome of turmeric(Curcuma tonga),has been recognized as a potent anticancer and chemo-preventative ***,its clinical application for cancer treatment has been greatly limited due to its poor water-solubility and low *** this study,an amphiphilic copolymer based on Pluronic F68 conjugated with CUR(F68-CUR) was designed and synthesized as the carrier to tackle this *** stable micelles with CUR distributed in the core were formulated via solvent evaporation method,as confirmed by FIRT and *** the result of physicochemical characteristics of F68-CUR conjugate micelles,high drug conjugation rate(0.248 mg CUR/1 mg F68) was achieved,and the average particle size was115.2±3.0 nm with zeta potential of 11.5=1=0.6 ***,compared with free CUR,a significantly higher cytotoxicity of F68-CUR conjugate micelles against human breast cancer MDA-MB-231 cell line was *** IC50 of F68-CUR conjugate micelles was 1.5-fold tower than that of free CUR,indicating that enhanced antitumor activity of F68-CUR conjugate micelles was significantly *** together,these results suggested that F68-CUR conjugate micelles would be promising to improve the clinical outcome of CUR for cancer treatment.

关键词： curcumin conjugate micelles anticancer activity

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Gambogic Acid loaded pH-sensitive Mixed Micelles for Overcoming Breast Cancer Resistance

Gambogic Acid loaded pH-sensitive Mixed Micelles for Overcom...

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2014中国药物制剂大会——中国药学会药剂专业委员会年会、第六届亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Shengpeng Wang Yu Yang Jinming Zhang Yitao Wang Meiwan Chen State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of Macau

Multidrug resistance(MDR) is one of the major obstacles for successful treatment of breast *** of drug efflux transporters such as P-glycoprotein(P-gp) and anti-apoptotic proteins like survivin are the major reasons responsible for ***,a gambogic acid(GA)-loaded mixed micelle system made of poly(lactic-co-glycolic acid)-b-poly(L-histidine)-b-polv(ethylene glycol)(PLGA-pHis-PEG) and D-a-tocopheryl polyethylene glycol 1000(TPGS) was developed for overcoming MDR by the integrated effects of the pH-sensitive behavior of PLGA-pHis-PEQ P-gp inhibiting activity of TPGS and survivin downregulation ability of *** resulting GA-loaded mixed micelles were stable at pH 7.4,while dissociated in a weakly acidic environment(pH 5.5) and released the incorporated GA *** GA-loaded mixed micelles increased the cell cytotoxicity against both drug-sensitive human breast MCF-7 and drug-resistant MCF-7/ADR *** IC50 of The GA-loaded mixed micelles against MCF-7/ADR cells was 3-fold bwer than that of free GA,which was associated with the enhanced apoptosis and cell arrest in the G0/G1 ***,the GA-baded mixed micelles enhanced the fluorescence intensity of rhodamine 123,decreased the intracellular ATP levels,downregulated the expression of survivin,indicating that this system could target distinct mechanisms to overcome breast cancer resistance.

关键词： gambogic acid breast cancer pH-sensitive mixed micelles P-glycoprotein surviving

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iRGD decorated lipid-polymer hybrid nanoparticles for targeted co-delivery of doxorubicin and sorafenib to enhance anti-hepatocellular carcinoma efficacy

iRGD decorated lipid-polymer hybrid nanoparticles for target...

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2014中国药物制剂大会——中国药学会药剂专业委员会年会、第六届亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Jinming Zhang Jie Hu Guang Liang Yitao Wang Meiwan Chen State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of Macau School of Pharmaceutical Sciences Wenzhou Medical University

The combination of doxorubicin(DOX) with sorafenib(SOR) has been proved to be an effective strategy to enhance anti-hepatocellular carcinoma(HCC) ***,varied in vivo pharmacokinetic profiles and different endocytosis capacities of these two drugs greatly hinder their current *** solve these problems and enhance the anti-HCC efficacy,the tumor-targeting poly(lactic-co-glycolic acid)(PLGA)-lecithin-poly(ethylene glycol)(PEG) core-shell nanoparticles(NPs) decorated with a tumor-penetrating peptide iRGD were developed for DOX and SOR *** the drug ratio of DOX and SOR were optimized to reach the best synergistic anticancer effect in vitro,the stabilized iRGD-decorated hybrid NPs with DOX and SOR co-loaded(DOX+SOR/iRGD NPs) were *** the iRGD-integrin recognition,DOX+SOR/iRGD NPs showed synergistic cytotoxicity,pro-apoptotic ability and enhanced internalization rate in human liver cancer HepG2 *** vivo pharmacokinetic testing demonstrated that an extended circulation and bioavailability of DOX+SOR/iRGD NPs than free DOX+*** importantly,DOX+SOR/iRGD NPs significantly enhanced antitumor efficiency when observed in HCC xenograft mouse ***,this study provides a promising nanoparticulate drug co-delivery strategy to enhance anti-HCC efficacy of the combined clinical anticancer drugs.

关键词： Hepatocellular carcinoma Active targeting Doxorubicin Sorafenib iRGD peptide

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Mesoporous silica nanoparticles:structural design and biocompatibility

Mesoporous silica nanoparticles:structural design and biocom...

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2014中国药物制剂大会——中国药学会药剂专业委员会年会、第六届亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者：李晓溪 chunsheng Gao 中国人民解放军军事医学科学院 the Academy of Military Medical Sciences

Mesoporous silica nanoparticles（MSNs） are new material system at the end of 20 th *** have unique properties such as large surface area（000m2g-1）,large pore volume（cm3g-1）,controllable pore size（2～50 nm）,very narrow particle size distribution and open pore ***,MSNs are widely used in the field of drug delivery system,protein separation,adsorption,molecular sieving and *** mechanism is shown in *** of LCT mechanis m The synthesis of MSNs requires the participation of a templating agent,usually a surfactant in aqueous solution which is either neutral or *** acid or alkali condition,the template directs the polymerization of silicates from a precursor,typically an ester oforthosilicic ***,the template is removed by calcination or solvent *** control of particle size and morphology can be attained to control the relative rates of hydrolysis and condensation of the silica source,and the magnitude of the interactions between the growing silica polymer and the assembled *** can be controlled by choosing different templates,by controlling the pH of synthesis,and by using co-solvents or *** size and morphology of MSNs are usually assessed by electron microscopy and dynamic light *** important factors of the pore size and morphology are the relative amounts of silica source and surfactant in solution,and the packing capacity of the *** measurement include transmission electron microscopy,X-ray diffraction and nitrogen *** are more stable system compared with other biomaterials such as *** types of MSNs have been shown to be nontoxic in many biological system if they are prepared with certain optimized structural features and are applied at the right *** could be internalized by cells through *** cytotoxicity depend on concentration of MSNs,cell types,surfactant removal methods,particles size and morphology.

关键词： Mesoporous silica nanoparticles:structural design and biocompatibility

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Multifunctional polymeric micelles for MDR reversing

Multifunctional polymeric micelles for MDR reversing

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2014中国药物制剂大会——中国药学会药剂专业委员会年会、第六届亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Chengming Zhou Wenping Wang Yanhua Liu Department of Pharmaceutics School of PharmacyNingxia Medical University

Most of conventional chemotherapeutic agents used for cancer chemotherapy suffer from multidrug resistance(MDR) of tumor cells and poor antitumor *** on physiological differences between the normal tissue and the tumor tissue,one effective approach to improve the efficacy of cancer chemotherapy is to develop pH-sensitive polymeric micellar delivery *** targeting approaches has shown great potential to open a new era in cancer *** has been developed for improved the antitumor efficacy and reduced toxicity by increasing cellular accumulation and altering biodistribution of anticancer drugs through specific cell surface *** a targeting moiety to the surface of polymeric micelles,such as a ligand or an antibody,helps the efficient cellular uptake and improves drug retention in MDR tumor cells via receptor-mediated endocytosis,while avoiding P-gp efflux and being able to enhance the reversal of ***,the endosomal pH triggering anticancer drug release and the endosomal escaping activity of tumor intracellular pH-sensitive polymeric micelles allowed cytosolic delivery of anticancer drug,by avoiding drug sequestration mechanism in MDR cells and through bypassing MDR proteins expression on cellular *** the intracellular pH-triggered drug release is combined with receptor-mediated active targeting,the multifunctional polymeric micelles can not only recognize the cancer cells via receptor-mediated binding,but also release the drug at tumor sites,which internalized via receptor-mediated endocytosis followed by endosomal-pH triggered drug release inside the cells,which reverses multidrug resistance..The combined use of active targeting and intracellular pH-triggered quick drug release can significantly increase the intracellular drug concentration and efficiently kill tumor cells without any risk of developing drug ***,designing an advanced multifunctional polymeric micellar delivery system should b

关键词： Multifunctional polymeric micelles tumor targeting intracellular drug release MDR reversion

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Synthesis and evaluations of three folate analogue-lipid conjugates as the targeting materials for treatment of invasive breast cancer

Synthesis and evaluations of three folate analogue-lipid con...

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2014中国药物制剂大会——中国药学会药剂专业委员会年会、第六届亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Rui-Jun Ju Wan-Liang Lu School of Pharmaceutical Sciences Peking University

Objective:Specific binding between ligand and receptor is used as a targeting strategy to enhance the accumulation of drug-loaded liposomes in the cancer *** receptor has been found to be overexpressed on invasive breast cancer *** the present study,three kinds of folate analogue-lipid conjugates were synthetized and evaluated as the targeting ligands of folate receptor for modifying drug-toaded liposomes to improve the efficacy in treatment of invasive breast ***:Three folate analogues,aminopterin,pemetrexed and raltitrexed,were selected as the targeting molecules and were conjugated with N-hydroxysuccinimidyl-polyethylene glycol distearoylphosphatidyl ethanolamine(DSPE-PEG2000-NHS).The synthesized conjugates were confirmed by a matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS).Nanostructured targeting liposomes were subsequently developed by incorporating these targeting conjugates onto the surface of liposomes,*** was used as the anticancer agent and encapsulated into these liosomes by ammonium gradient *** were made by measuring particle sizes,polydispersity indexes and encapsulation efficiencies of three targeting epirubicin *** vitro cellular uptake,and cytotoxicity were performed on the invasive breast eaneerMDA-MB-231 celfe and less invasive breast cancer MCF-7 ***:All folate analogues were successMly conjugated with DSPE-PEG2000-NHS and modified onto the liposomes as the targeting materials,*** varying types of targe ting epirubicin liposomes,particle sizes were approximately 100 nm,zeta potentials were slightly negative,and their encapsulation efficiencies were >95%.Results from the cellular uptake indicated that three targeting materials could enhance the ceUular uptake of epirubicin in both kinds of cancer *** from cytotoxicity revealed that all of three targeting epirubicin liposomes exhibited stronger ef

关键词： Folate analogue-lipid conjugates targeting materials invasive breast cancer

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A safe and efficient hepatocyte-selective carrier system based on myristoylated preSl/21-47 domain of hepatitis B virus

A safe and efficient hepatocyte-selective carrier system bas...

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2014中国药物制剂大会——中国药学会药剂专业委员会年会、第六届亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Quan Zhang Tijia Chen Xun Sun Tao Gong Zhirong Zhang West China School of Pharmacy Sichuan University

A safe and efficient liver targeted PEGylated liposome(PEG-Lip) based on N-terminal myristoylated preS1/21-47(preS1/21-47myr) of hepatitis B virus was successfully *** study aimed to elucidate the cellular uptake mechanism of preS1/21-47 myr modified PEG-Lip(preS1/21-47myr-PEG-Lip) in hepatogenic cells and the distribution behavior of preS1/21-47myr-PEG-Lip in Vr:CDl(ICR) *** cellular uptake results showed preS1/21-47myr-PEG-Lip were effectively uptaken by hepatogenic cells(including primary hepatocytes and Hver tumor cells) through a receptor-mediated endocytosis pathway compared with non-hepatogenk *** systemic administration to H22 hep atoma-bearing mice,preS1/21-47myr-PEG-Lip showed significant liver-specific delivery and an increase in the distribution of preS1/21-47myr-PEG-Lip in hepatic ***,no acute systemic toxicity and immunotoxicity were observed after intravenous injection ofpreS1/*** Hver toxicity was observed despite the dramatic increase of preS 1/21-47 myr-PEG-Lip in *** results demonstrated that the preS 1/2l-47myr-PEG-Lip could be a promising carrier system for targeted hver disease therapy and imaging.

关键词： PreS1/21-47myr Liver-targeted delivery system PEGylated liposomes Hepatogenic cells Differentiation

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