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检索条件"任意字段=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"

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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...

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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：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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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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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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Charge-conversional PLGA nanoparticle to active deliver chemotherapy drug to tumor

Charge-conversional PLGA nanoparticle to active deliver chem...

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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： Jiang-bo Du Dao-zhou Liu Bang-le Zhang Si-yuan Zhou Department of Pharmaceutics School of PharmacyFourth Military Medical University

Poly(lactic-co-glycolic acid)(PLGA) nanoparticles are widely used in tumor targeted drug delivery system owing to its non immunogenicity and biodegradable ***,the naked PLGA nanoparticles not only have low drug loading but also can be rapidly removed from blood circulation by the immune ***,the aim of this study was to focus on the preparation of both active and passive tumor targeting lipid hybrid PLGA nanoparticles(LNPs) to enhance drug loading and drug delivery ***-ARG-HIS-OMe and DSPE-PEG-FA were synthesized and were used to prepare DOX-baded LNPs by emulsion-solvent evaporation *** particle size,drug loading and encapsulation rate of naked PLGA nanoparticles was 162 nm(detected by DLS),2.55%and 22.0%,*** particle size,drug bading and encapsulation rate of LNPs was 191 nm(detected by DLS),10.20%and 86.4%,*** LNPs showed core-shell *** X-ray photoelectric spectrometer analysis indicated that FA and ARG-FflS-OMe were localized on the surface of ***7.4 medium,DOX-baded LNPs showed negatively charged and released DOX *** pH5.0medium,DOX-baded LNPs showed positively charged and released DOX ***-baded LNPs had not effect on the bbod red cell membrane in pH7.4 medium,and it severely destroyed the bbod red cell membrane in pH5.0 *** with free DOX,DOX-baded LNPs delivered more DOX to the nucleus of KB cells and MBA-MD-231/ADR ***-baded LNPs induced more apoptosis on KB cells,A549 cells,MBA-MD-231 cells and MBA-MD-231/ADR cells as compared with free *** with the naked PLGA nanoparticles and free DOX,DOX-baded LNPs significantly inhibited the proliferation of A549 cells,KB cells,MBA-MD-231 cells and MBA-MD-231/ADR ***-baded LNPs showed great cytotoxicity on folate receptor overexpressed tumor *** with 5 mg/kg free DOX,the same dose of the DOX-baded LNPs significantly inhibited the growth of tumor in tumor bearing nude mice(i

关键词： PLGA doxorubicin lipid hybrid nanoparticles folate pH-sensitive

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HCPT/DOX dual-drug Nanoparticle Demonstrate Synergistic Therapeutic Effect to MCF-7 Cells through Improved Cellular Accumulation

HCPT/DOX dual-drug Nanoparticle Demonstrate Synergistic Ther...

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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： Fei Chen Yuanyuan Zhao Yuanming Pan Xiangdong Xue Xu Zhang Kumar Anil Xing-Jie Liang CAS Key Laboratory for Biological Effects of Nanomaterials & Nanosafety National Center for Nanoscience and Technology

10-Hydroxycamptothecin(HCPT) and doxorubicin(DOX) are inhibitors of topoisomerase Ⅰ and topoisomerase Ⅱ***,combination therapy using HCPT and DOX is possible and significant to clinic applicatioa Unfortunately,different pH of their commercial injections prevents the simultaneously *** with simply mixture in application due to the possible ***,we developed a "green",carrier free method to fabricate pure chemotherapeutical nanoparticles with uniform shape and size by co-aggregation of HCPT and DOX(HD NPs).Through delicate controlling the preparation process,optimizing reaction time and molar ratio of DOX to HCPT at certain drug concentrations,we can obtain spherical dual-drug nanoparticles with uniform *** to the traditional drug delivery system,the pure chemotherapeutical nanoparticles have the following advantages:(i) The preparation process is not only "green" but also simple,and all the reagents applied here are FDA approved,which will benefit to its practical applicatioa(ii) Avoid biosafety uncertainties brought by employing conventional nanocarriers.(iii) Enhanced therapeutic efficiency of HCPT/DOX to breast cancer by dual-drug nanoparticles through improved cellular uptake,(iv)HD NPs can act as self-indicating drug delivery system(SIDDS) upon *** this study integrated HD dual-drug particles changed the CI index and combination effect of H/D mixture from antagonism to synergism,which show us again the attractive advantages of *** confocal fluorescence comparision and flow cytometry analysis,HD nanoparticles improved the drugs cellular uptake and *** HPLC quantification result,HD nanoparticles improved the nuclear uptake of HCPT as high as 1.57 folds in comparison to free HCPT itself Furthermore,HD nanoparticles demonstrate enhanced synergistic therapeutic effect in *** contrast to reduced effect of physical mixing of HCPT and DOX solution,the obtained HD NPs with integ

关键词： HCPT/DOX dual-drug Nanoparticle Demonstrate Synergistic Therapeutic Effect to MCF-7 Cells through Improved Cellular Accumulation DOX MCF

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Multi-targeting delivery of doxorubicin in tumor cells by saturated fatty acid based pH-sensitive micelle

Multi-targeting delivery of doxorubicin in tumor cells by sa...

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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： Han Cui Meng-lei Huan Bang-le Zhang Si-yuan Zhou Department of Pharmaceutics School of PharmacyFourth Military Medical University

Doxorubicin(DOX) is a commonly-used chemotherapy drug for tumor ***,the severe side effect,tow selectivity and multiple drug resistance(MDR) hinder its clinical ***,DOX shows a high affinity to DNA and ***,DNA intercalation is not the only mechanism of the antitumor activity of *** multiple interactions can occur between mitochondria and DOX,which induce the mitochondrial ***,mitochondria specific DOX delivery system can change DOX sub-cellular distribution route and reverse *** was reported that(3-carboxypropyl)triphenyl- phosphonium(TPP) exhibited mitochondrial targeting characteristic due to its high lipophilicity and stable cationic *** theory,DOX can be delivered to mitochondria by conjugating TPP with *** fatty acids are safe and abound of hydrophobic material in *** order to attenuate non selective toxicity and overcome the MDR,a series of saturated fatty acid based pH-sensitive amphiphilic polymer and mitochondria-specific conjugate TPP-DOX was synthesized,and a new pH-sensitive micelle was prepared to deliver DOX to nucleus and mitochondria *** loaded micelle were prepared by emulsion-solvent evaporation *** released from FA-PEG-hyd-PA micelle showed a pH-dependent *** TPP-DOX showed tower cytotoxicity than free DOX on KB cells,A549 cells,Hela cells,HUVEC cells and HEK293 cells,but it showed higher cytotoxicity than free DOX on DOX-resistant MDA-MB-231/ADR ***-DOX/DOX loaded FA-PEG-hyd-PA micelle induced the more apoptosis in KB cells,A549 cells,and MDA-MB-231/ADR cells than DOX loaded FA-PEG-hyd-PA ***-DOX/DOX loaded FA-PEG-hyd-PA micelle showed the higher cytotoxicity against A549 cells,KB cells,Hela cells and MDA-MB-231/ADR cells than DOX loaded FA-PEG-hyd-PA *** microscopy confirmed that TPP-DOX/DOX loaded FA-PEG-hyd-PA micelle respectively delivered TPP-DOX and DOX to the mitochondria and nucleus simultaneo

关键词： doxorubicin multiple drug resistance (3-carboxypropyl)triphenylphosphonium mitochondria pH-sensitive micelle

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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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Self-assembled polymersomes for effects of PM-OM on the expression of a-SMA and collagen-I in HSCs

Self-assembled polymersomes for effects of PM-OM on the expr...

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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： Jianhong Yang Yanhui Hou Jianhai Chen School of Pharmacy Ningxia Medical University Department of pharmaceutical science Nanfang HospitalSouthern Medical University

Introduction:Oxymatrine（OM） is a kind of alkaloid extracted from a Chinese herb that has been found to possess anti-hepatic fibrosis effect,but its anti-fibrotic potential may be limited due to a lack of a short half-life period and adverse ***（PM）assembled from amphiphilic bbck copolymers represent promising vesicles for *** aim of this study was to devebp a novel drug carrier based on PM and evaluate anti-fibrosis effects of OM-loaded on the expression of a-SMA and collagen-I by Western blotting in ***:Polymersomes were prepared using films hydration as reported by Discher et *** MPEG-PCL and Maleimide-PEG-PCL bbck copolymers were synthesized by ring-opening polymerization of ε-CL using MPEG or Maleimide-PEG as the initiator in the presence of stannous octoate as a catalyst,and method described in full detail *** is foaded into polymersomes（PM-OM） by a pH-gradient method devefoped for *** were isolated from livers of male Wistar rats as described *** being incubated with for the indicated periods,HSCs were washed with ice-cold PBS and lysed with cell lysis buffer and 1 mM *** cell membrane was sonicated briefly and *** supernatant was the whole cell ***,the protein samples were subjected to Western bbtting as described ***:A series of PM based on polyethylene glycoI)-b-poly（e-caprolactone）(PEG-b-PCL) were prepared and *** was baded into PM by a pH-gradient *** average drug loading of PM-OM,with a size of 95 nm,was 6.8%.The expression levels of a-SMA and collagen-I were decreased in the PM-OM and the OM *** the PM-OM and OM groups compared to the nomal group,the levels of a-SMA were reduced to 61.28%and 13.1%,respectively and collagen-I was reduced to 56.7%and26.9%,***:In this work,a novel anti-fibrosis drug delivery system with high drug-bading efficacy was ***-OM displayed significantly reduced the expr

关键词： Self-assembled polymersomes for effects of PM-OM on the expression of a-SMA and collagen-I in HSCs SMA

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