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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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Study On The Her-2 And Cd44 Receptors Mediated Ha/Tpgs2k Mixed Micelle Delivery System

Study On The Her-2 And Cd44 Receptors Mediated Ha/Tpgs2k Mix...

引用

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：陈大为沈阳药科大学药学院药剂系

In this study,hyaluronic acid(HA),which targeted to the CD44 receptor,was used as the hydrophilic ***-(L-histidine)(PHis) with pH-sensitive characteristic was used as the hydrophobic *** designed and synthesized a series of new HA-g-PHis polymer(HA-PHis)with different degrees of substitutioa Polyethylene glycol 2000(PEG2000),chosed as the hydrophilic chain,was reacted with d-a-tocopherol succinate(VES) to generate TPGS2 *** had bng circulation and reversing multidrug resistance(MDR) function Furthermore,TPGS2 k was successfully modified by Her-2 peptide to prepare the pep-TPGS2 ***-PHis polymer based multifunctional polymer micelle systems were prepared for intracellular delivery of doxorubicin(DOX).Pharmaceutics properties,cytotoxicity,cell uptake,uptake mechanisms and reversing MDR mechanisms were further researched as well as in vivo pharmacokinetics,pharmacodynamics,and animal imaging in ***-loaded HA-PHis single micelles and HA-PHis/TPGS2 k and HA-PHis/pep-TPGS2 kmixed micelles were prepared by ultrasonic *** pharmaceutical properties of polymeric micelles were further *** results showed that drug encapsulation efficiency of different polymer micelles ranged from 89%to 93%,and particle size was between 154 and 187 nmDOX-loaded HA-based polymeric micelles presented spherical micellar nanoparticle with uniform *** potential was about-11.6 to-13.4 *** vitro release behavior of polymeric micelles were investigated by dynamic dialysis micelles,and the results showed that these plymeric micelles were obviously pH-sensitive,and the release rate significantly accelerated whenpH was close to lysosomal acid condition Human breast cancer MCF-7 cell with CD44 receptor highly expressed was selected as a cell ***,cellular uptake and uptake mechanism of the DOX loaded HA-PHis micelles(HPHM) were *** showed stronger cytotoxicity in vitro compared with free doxorubicin solution,and the cytotoxicity of micell

关键词： HA-PHis Her-2 peptide TPGS2k pH-trigger release polymer micelles doxorubicin multidrug resistance uptake mechanism in vivo anti-tumor activity

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Which one is better for cancer therapy:Augmenting the EPR effect or normalizing angiogenesis

Which one is better for cancer therapy:Augmenting the EPR ef...

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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： Dan Wang Jijun Fu Binlong Chen Dong Peng Lan Yuan Bing He Wenbing Dai Hua Zhang Xueqing Wang Qiang Zhang State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking University

At present,more and more cases about regulation of angiogenesis as auxiliary treatment of chemotherapy have been *** application of anti-angiogenic agents can restore the balance and revert the vasculature to a more normal ***,vascular normalization is in conflict with the EPR effect that is the golden principle which many drug delivery systems is based *** clear this confusion,two tumor models had been estabilished to evaluate which one is superior in cancer therapy,augmenting the EPR effect or normalizing the *** had been validated that THE) could modulate angiogenesis on KM mice bearing S-180 sarcoma xenografts using Multispectral Optoacoustive Tomography and Immunofluorescence:lower concentrations enhancing endothelial sprouting while higher ones stimulating vessel maturatioa Then two tumor models had been set up by different doses and rhythm of THD:the EPR effect augmented model with more chaotic blood vessels(Model A) and vascular normalization model with more normal angiogenesis(Model B).Then,small molecules doxorubicin,doxorubicin liposomes,doxorubicin liposomes with high binding affinity to angiogenesis(RGD modified liposomes) and liposomes with high binding affinity to tumor tissues(7PEP modified liposomes) had been prepared to compare the degree of extravasation from the tumor blood *** distribution of drugs and tumor vasculature were visualized by laser-scanning confocal microscopy in more *** images qualitatively presented the distribution of drugs in tumor tissue:the amount of small molecules in tumor tissues increased in both models compared with base line,while there was more obvious extravasation of liposomes from the tumor blood vessel in Model A than in Model B regardless of liposomes with low or high binding *** data quantitatively showed the body distribution and tumor accumulation of *** extravasation of small molecules had been measured in both models,but for lipo

关键词： Which one is better for cancer therapy:Augmenting the EPR effect or normalizing angiogenesis EPR

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A Novel EGFR mAb Modified Cationic Lipoplex for pulmonary delivery of survivin-siRNA

A Novel EGFR mAb Modified Cationic Lipoplex for pulmonary de...

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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： Qin Chen Dan-Feng Shi Qing-Ri Cao Jing-Hao Cui College of Pharmaceutical Science Soochow University

Survivin,a member of the inhibitor of apoptosis proteins family,plays an important role in cancer cell apoptosis and proliferation *** order to prepare survivin-siRNA loaded lipoplexes for pulmonary administration,a novel Lipidoids(epoxy alkyl amine derivative,EAADs) was *** fabricated EAADs lipoplex has a uniform particle size about 200 nm with low cell toxicity and improved anti-RNase *** aerodynamic diameter of spray dried powder of EAADs lipoplex can meet the requirement of pulmonary *** of confocal laser scanning microscope revealed that A549/DDP cells treated with EGFR mAb-PEG-EAADs-3lipoplex has a relative uniform distribution and a significant increase of FAM-siRNA signals in the cytoplasm not overlapped with the lysosome signals while compared with Lipofectamine 2000 *** result indicates that an enhanced cytoplasm localization and lysosome escape efficiency of siRNA transfected by EGFR mAb-PEG-EAADs-3 carriers compared with Lipofectamine 2000(Fig.1).Moreover,our EGFR mAb-PEG-EAADs-3 lipoplex has an interesting property to avoid the uptake of macrophage and mainly locate in the cytoplasm of A549 cells in our established A549 cells & Raw 264.7 cells co-culture system,which will benefit for the efficacy of siRNA in vivo for cancer *** vitro pharmacodynamics on A549/DDP cells shows that after transfected with survivin siRNA by different vectors such as EAADs-3,PEG-EAADs-3,EGFR mAb-PEG-EAADs-3,both of the sensitivity of cisplatin to A549/DDP cell and apoptosis rate were increased but the survivin protein expression was down-regulated(Fig.2).In vitro pharmacodynamics data of PEG-EAADs-3 was improved compared with Lipofectamine 2000,especially for EGFR *** summary,EGFR mAb-PEG-EAADs-3 lipoplex has a promising potential of siRNA delivery by pulmonary administration to reverse tumor resistance co-administrated with chemotherapy drug.

关键词： EAADs Lipoplex Dry powder inhalation Survivin A549/DDP

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c(RGDfK)-coated,biotin-functionalized ultras mall Fe3O4 nanoparticles and their targeting to integrin αvβ3-rich tumor cells

c(RGDfK)-coated,biotin-functionalized ultras mall Fe3O4 nano...

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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： Jialiang Lin Bing He Wenbing Dai Hua Zhang Xueqing Wang Qiang Zhang State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking University

The applications of superparamagnetic iron oxide nanoparticles(SPIONs),especially in the biomedical field,is rapidly increasing for tumor diagnosis and ***,two problems are common confronted when applying these particles in vivo:(1) conventional SPIONs have severely nonspecific uptake by non-target cells under the action of an external magnetic field,which weakens the targeting efficiency of SPIONs;(2) at size less than 15 nm,the particles have very limited drug-loading capacity which undermines the curative effect ***,we present a direct synthesis of ultrasmall Fe304 NPs(<10nm).The surfaces of ultrasmall Fe304 NPs are bonded with c(RGDfK)-PEG2000-Dopamine and ***,as high affinity anchor group for SPIONs,connect c(RGDfK)-PEG2000-Dopamine/Biotin-PEG2000-Dopamine to *** present three-step targeting procedure(see Figure 1):The first step is to inject c(RGDfK)-coated,biotin-functionalized SPIONs,the second step is to inject(Strept)avidin,the final step is to inject DOX-Biotin conjugate or biotinylated DOX *** Fe304 NPs with 6 nmcore size were synthesized by microwave synthesis method.c(RGDfK) peptides,and biotin were conjugated onto one distal end of the PEG2000 *** the other distal end of the PEG2000 arms,dopamines were *** process of c(RGDfK)-PEG2000-Dopamine and Biotin-PEG2000-Dopamine is shown in Figure *** expect that c(RGDfK)-PEG2000-Dopamine conjugated SPIONs will exhibit a higher level of cellular uptake than cRGD-free ones in *** to strong affinity of(Strept) avidin with biotin,we expect that Biotin-PEG2000-Dopamine conjugated SPIONs will exhibit a higher level drug-loading capacity and tumor targeting efficiency in vivo.

关键词： RGDfK coated,biotin-functionalized ultras mall Fe3O4 nanoparticles and their targeting to integrin rich tumor cells

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Dll4-targeted nanomedicine for antiangiogenic cancer therapy

Dll4-targeted nanomedicine for antiangiogenic cancer therapy

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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：刘亚蓉 Ying-Yun Guan Xin Luan Hong-Zhuan Chen Chao Fang 上海交通大学医学院 Department of Pharmacology Institute of Medical SciencesShanghai Jiao Tong University School of Medicine

Inhibiting tumor-associated angiogenesis is a validated major strategy in cancer *** drug targets desired to be excavated for the poor response and resistance of the early antiangiogenic ***,D114-Notch signaling pathway has emerged as a critical regulator of the development and maintenance of tumor ***-like ligand 4(DU4),the only Notch ligand to be selectively over-expressed on endothelial cells,is involved in tumor ***,DIM is a negative-feedback regulator of angiogenesis and strongly upregulated in tumor ***,a new nano medicine,GD16 peptide conjugated,D114 targeted biodegradable nanoparticles loading paclitaxel(GD16-PTX-NP),was developed for antiangio genie ***16 was isolated from a phage display peptide library,which can bind D114over-expressed in tumor neovasculature with high affinity and *** using D114-negative FaDu xenografts,the D114 targeting efficacy in tumor vessel of GD16-PTX-NP and the antiangio genic therapy of FaDu xenograft were *** and Results GD16-PTX-NP were fabricated by emulsion and solvent evaporation method with a following surface ***16-PTX-NP were determined using a Zetasizer Nano ZS instrument and had a hydrodynamic size of 189 nm,and zeta potential of-14.2 *** nanoparticles were spherical in shape with a smooth surface shown in *** vitro release experiments,the drug was released in a biphask pattern in *** blood clearance curves indicated that the nanoparticles displayed improved pharmacokinetic profiles compared with PTX solution(Fig.1).The cellular uptake was assayed on the *** intracellular accumulation of GD16-NP in HUVEC could be dramatically inhibited by excess free GD16,low temperature and in the presence of phenylarsine oxide and filipin(Fig.2).It is dramatically shown that DiR-labeled GD16-NP accumulated more in the FaDu tumor tissue than DiR-labeled NP and the in vivo tumor targeting accumulatio

关键词： PTX Dll4-targeted nanomedicine for antiangiogenic cancer therapy

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The artificial neural network model of interaction between small molecules and serum albumin

The artificial neural network model of interaction between 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： Yan Chen Bo Tao Zongning Yin Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan University

The combination of protein and small molecule drugs significantly affects the uptake,transport,metabolism and excretion of drugs,further determines the stability and toxicity of ***,the interaction between the small molecule drugs and protein is important for understanding the effect of in vivo processes..Three crucial parameters of interaction between small molecules and serum albumin are binding constants,binding sites and the binding *** relationship between molecular descriptors of small molecule drugs and the parameters of interaction between small molecules and serum albumin were calculated by artificial neural network *** we could obtain binding constants,binding sites and binding distances of unknown compounds by calculation according to the *** interaction of protein with unknown compounds,predicted by these parameters,can be used to guide the design of drug to avoid side effects caused by the improper binding of drug and *** this purpose,three artificial neural network models were established by back propagation network to predict the interaction between small molecules and serum *** synthesized new compounds A and B by carbon chains increasing reaction of benzyl bromide and ethyl *** using spectrophotometer,we measured three crucial parameters,which revealed the interaction between the new compounds and serum *** artificial neural network models predicted that the binding sites of compounds A and B with serum albumin were 0.93378 and 0.87414,binding constants were 7.86x1012 L×mol-1s-land5.49x1012 L×mol-1s-1,the binding distances were 3.544 nm and 1.881 *** by experiment,the binding sites of compounds A and B with serum albumin were0.9132 and 0.8017,the binding constants were 7.46x1012 L mol-1s-land 5.42 ×l012L mol-1s-1,the binding distances were 3.58 nm and 1.82 *** theoretical calculating values of three crucial parameters calculated by the three artificial neural network model

关键词： binding constants binding sites the binding distances artificial neural network interaction between small molecules and serum albumin

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The use of α-Conotoxin ImI to actualize the targeted delivery of paclitaxel micelles to α7 nAChR-overexpressing breast cancer

The use of α-Conotoxin ImI to actualize the targeted delive...

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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： Dong Mei Zhiqiang Lin Wenbing Dai Hua Zhang Xueqing Wang Wanliang Lu Qiang Zhang State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking University

Alphα7 nicotinic acetylcholine receptor(α7 nAChR),a ligand-gated ion channel,is extensively expressed in various tumor cells and involved in regulation of cell proliferation,angiogenesis,apoptosis,migration,invasion and secretion,making it to be a new valuable molecular target for the therapy of cancers.a-Conotoxin Iml,a disulfide-rich toxin purified from the venom of Conus imperialis,blocks homomeric alpha 7 nicotinic receptors with high apparent *** micelles(PMs),a type of self-assembled nanoparticles from amphophilic block copolymers,possess several strong superiorities as pharmaceutical drug carriers,such as biodegradability,small particle size,prolonged circulation,as well as preferential accumulation in the tumor sites through EPR effect and active *** an attempt to actualize the targeted delivery to the cancer cells overexpressing α7 nAChR,herein,a-conotoxin Iml was modified on the PEG-DSPE micelles(Iml-PMs) for the first *** functioned carriers were spherical nanoparticles about 20 nm with negative charge and high drug encapsulation,and the ligand modification did not induce significant *** the confirmation of α7 nAChR expression in three cell lines including MCF-7 cells by immunofluorescence,the ligand-receptor interaction was monitored by fiuo-3/AM fluorescence imaging *** binding activity of Iml was still remained after chemical conjugatioa It was found that Iml-PMs could specifically deliver to α7 nAChR overexpressing MCF-7 cells in vitro and in vivo,not only more,but also faster compared with its unmodified control,via an α7 nAChR-mediated *** ligand-receptor interaction seemed *** of exhibiting greater cytotoxicity and inducing more cell apoptosis in vitro,paclitaxel loaded Iml-PMs displayed stronger antitumor efficacy in MCF-7 tumor-bearing nu/nu ***,the active targeted system showed low systemic toxicity and myelosuppression evidenced by less changes in body weigh

关键词： nAChR-overexpressing breast cancer The use of Conotoxin ImI to actualize the targeted delivery of paclitaxel micelles to

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Preparation and evaluation of Baicalin SLN across the BBB

Preparation and evaluation of Baicalin SLN across the BBB

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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：刘志东 Li Zhang Hainan Zhao Boli Zhang Weisan Pan The Institute of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine School of Pharmacy Shenyang Pharmaceutical University

The OX26-PEG-CSLN was prepared by the emulsion evaporation-solidification at low temperature method and mercaptan modification *** average particle size of OX26-PEG-CSLN was 47.68±1.65 nm and the zeta potential was-0.533±0.115 *** drug encapsulation efficiency of OX26-PEG-CSLN was 83.03±0.17%and the drug loading was 2.90±0.01%.The average number of 0X26 conjugated per nanoparticles was calculated to be 121±*** TEM micrographs showed that the morphologies of OX26-PEG-CSLN were spherical,and the nanoparticles were surrounded with gold particles indicating the presence of 0X26 conjugated to the surface of the *** immuno staining could also prove the remaining of biological activity of 0X26 following this *** results of NMR are consistent with the PEG-CSLN successfully conjugated with 0X26 *** results of X-ray diffractometry illustrated that baicalin were dispersed as molecular state in *** experiments showed that OX26-PEG-CSLN has stable characteristics in *** fluid pharmacokinetic experiment showed that the AUC value of OX26-PEG-CSLN was 11.08-fold comparing with that of the SOL(P<0.01),and the Cmax value of 0X26-PEG-CSLN was 7.88-fold comparing with that of the SOL(P< 0.01).Judging from the results of cell experiments,the uptake of OX26-PEG-CSLN in BMEC cells of rats were significantly more than that of CSLN,indicating that the conjugation OX26 on PEG-CSLN enhanced targeting features *** distribution experiment explained that the time to peak concentration of FP-CSLN and FP-OX26-PEG-CSLN was shortened and the growth of the peak value was *** concentration of drug maintained in a high level at 4h and eliminated *** fluorescence intensity of FP-OX26-PEG-CSLN were significantly improved compared to FP and FP-CSLN at 8h and could detect at 12 h and 24 h,which explains the function of prolonging action time of drug *** vivo imaging experiment s

关键词： Baicalin Pegylation OX26 Cationic solid lipid nanoparticles brain targeted drug delivery system

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Preparation,Characteristics of Large porous Cyclosporine A/Quaternized Chitosan/Hydroxypropyl-β-Cyclodextrin Microspheres for Inhalation

Preparation,Characteristics of Large porous Cyclosporine A/Q...

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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： Cui Liu Qinxin Zhao Qianwen Zhang Huanyu Zang Zhongrui Zhang Qihua Sun Zijing Yu Zhanqin Feng Wei Fen Zhang Clinical Undergraduates of Class 18 Grade 2011 Basic College of Weifang Medical University College of Pharmacy and Biological Science Weifang Medical University

Pulmonary sustained delivery is becoming a novel drug delivery system which has attracted much attention in recent ***（Large Porous Particles,LPPs）with the diameter larger than 5 μm,the density less than 0.4 g/cm are considered to have more advantages for pulmonary drug delivery *** this study,inhalable LPPs were designed to reduce side effects,provide drug protection and to sustained release Quaternized Chitosan（HTCC） and Hydroxypropyl-β-cyclodextrin（Hp-β-CD）were applied to develop large porous microspheres for pulmonary delivery by spray drying method,while the cyclosporine A（CsA） was used as a model *** physiochemical characteristics such as morphology,drug loading,and encapsulation efficiency were *** results of Scanning Electron Microscope showed the microspheres were spherical with smooth or wrinkled surface surfaces,and with the diameters between 0.5～7 μm The drug entrapments of microspheres A-I were from5.77%to 7.28%,and encapsulation efficiencies were from 0.89%to 1.85%,*** microspheres possessed low tap densities（< 0.48 g/cm） and could effectively reduce the *** results suggested that Cyclosporine A/Quaternized Chitosan/Hydroxypropyl-P-cyclodextrin microspheres were a promising carrier for pulmonary delivery.

关键词： Quaternized Chitosan Hydro xypropyl-β-cyclodextrin Large Porous Particles Cyclosporine A Spray-drying Pulmonary delivery

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Pullulan and poly(β-amino) ester-containing nanoparticles for the hepatoma-targeted co-delivery of gene and chemotherapeutic agent

Pullulan and poly(β-amino) ester-containing nanoparticles f...

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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： Yuanyuan Liu Yan Wang Ning Zhang Yinsong Wang Tianjin Cancer Institute and Hospital Research Center of Basic Medical Science & School of PharmacyLaboratory of Breast Cancer Prevention and TherapyMinistry of EducationTianjin Medical University

Objective:Poly(β-amino) esters(PBAEs) exhibit great potential as gene delivery reagents because they are easily synthesized and exhibit the relatively low toxicity and high transfection efficiencies in a wide variety of cell ***(PL) is a water-soluble,non-toxic,non-immunogenic,non-mutagenic and non-carcinogenic nature polysaccharide which produced by Aureobasidium *** to its excellent biological and physicochemical features,pullulan has become an attractive ingredient for many pharmaceutical applications and chemical *** investigations have shown that pullulan has a liver-targeting capability because of its high affinity for the asiaoglycoprotein receptor(ASGPR).This study designs a novel pullulan and poly(β-amino) ester-containing nanoparticle carrier of gene and chemotherapeutie agent for their hepatoma-targeting ***:PBAE(amine-terminated C32) was synthesized by Michael-addition reaction Plasmid DNA expressing green fluorescent protein(pEGFP),as a model gene,was condensed with cationic PBAE to form PBAE/pEGFP *** drug,methorexate(MTX),was conjugated to pullulan via ester bond to synthesize polymeric prodrug of ***,MTX-PL was coated on the surface of PBAE/pEGFP polycomplex via adsorption to form MTX-PL/PBAE/pEGFP *** specific affinity of MTX-PL for ASGPR that overexpressed in HepG2 cells was assessed by the ligand competition binding *** in vitro transfection efficiency of MTX-PL/PBAE/pEGFP nanoparticles was qualitatively and quantitatively analyzed by the fluorescence microscopy and the flow cytometer,and their cytotoxicity in HepG2 cells was measured using Cell counting kit-8(CCK-8) *** that,in vivo imaging technique was used to further assess the hepatoma-targeted delivery of MTX-PL/PBAE/pEGFP nanoparticles in HepG2 tumor-bearing nude ***:MTX-PL was successfully synthesized and showed a strong binding affinity for ASGPR on HepG2 ***-PL/

关键词： pullulan poly(β-amino) ester hepatoma-targeted gene chemotherapy agent

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