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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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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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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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The effect of intracellular rapid release behavior of PLGA microparticles as vaccine adjuvants on immune response

The effect of intracellular rapid release behavior of PLGA m...

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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： Qi Liu Lianyan Wang Xiaoming Chen Jilei Jia Weifeng Zhang Guanghui Ma National Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of Sciences

To provide protective immunity against infective diseases through immune-stimulation,rational design of vaccine adjuvants must be *** view of the potential use of targeting antigens to the APCs（antigen-presenting cells）,in particular to DCs（Dentritic cells）,which are the most prominent APCs,particulate delivery systems,especially microparticles（MPs）,have received considerable interest for application in antigen *** MPs encapsulating with antigens uptake by DCs,they get into the endosome/*** antigens could be released rapidly from MPs,they may escape into the cytoplasm,then being processed and bounded with MHC I molecules,finally induct CTL（cytotoxic T lymphocyte） *** to examine whether these intracellular rapid release behavior could affect immune response,we designed the MPs to realize this behavior by endowing the pH-responsive character adjusting the structure of MPs to the thinner shell and bigger inner space meanwhile co-encapsulating the antigen release helper molecules（specific inorganics）that interact with much proton in the endosome/lysosome of DCs（pH.0 and 6.5）and assist antigens in the internal water phase release and escape into the cytoplasm to generate following immunology *** prepared these designed uniform-sized PLGA MPs by SPG membrane emulsification and the average size was 1000 *** MPs were incubated in PBS at different pH values（pH.4,6.5 and 5.0） which imitated the intracellular presentation environment to test whether they possessed rapid release *** results showed these MPs released antigens in a pH-dependent way to confirm its excellent rapid release *** those fabrication and characterization,we performed the experiments to detect whether the MPs could influence the immune response on BMDC in *** results showed that the MPs could enhance cross-presentation and up-regulate expression of co-stimulatory markers and secretion of ***,ovalbumin（OVA） was used as model

关键词： Vaccine adjuvants PLGA microparticles Dentritic cells intracellular rapid release character immune response

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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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Thermosensitive hydrogel adjuvant based on quaternized chitosan induces effective humoral and mucosal immune responses

Thermosensitive hydrogel adjuvant based on quaternized chito...

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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： Qing-Ze Fan Jie Wu Yue-Qi Wang You-bin Wu Zhi-Guo Su Guang-Hui Ma National Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of Sciences1

Mucosal immune response builds a first barrier for the entry of the vast majority of pathogens which are transmitted through mucosa,such as influenza,Ebola,EV71 virus ***,mucosal vaccination offers unique advantages over parenteral vaccination such as simultaneous induction of mucosal and systemic immunization and convenience to *** particular,nasal mucosa is a potential portal of vaccine administration for its avoiding liver first-pass effect and gastric ***,the major obstacles of intranasal immunization are the short antigen residence time in nasal cavity caused by ciliary motion and the poor permeability of mucosa *** view of the above drawbacks,we devebped a thermosensitive cationb quaternized chitosan(HTCC) hydrogel as intranasal vaccine *** hydrogel is solutbn at room temperature,but transform to a gel-state when administrated intranasally,therefore probngs the antigen residence time in nasal *** addition,because of the penetration enhancer property of chitosan and its cationic modification,it may promote antigen penetration and subsequent uptake by *** examine the mechanism and efficacy of HTCC hydrogel adjuvant,we fabricated the HTCC hydrogel successfully through ionic cross linking ***,a non-invasive in vivo imaging method was used to evaluate the cy5 fluorescence labelled H5N1 antigen residence time in nasal cavity after *** showed a prolonged residence time of antigen with hydrogel adjuvant compared with antigen *** that,the expression quantity of nasal mucosal tight junction integrity protein ZO-1 was measured by immunofluoresence *** a result,HTCC hydrogel could reversibly damage ZO-1 protein and promote antigen penetration through mucosa,demonstrating hydrogel's ability of opening epithelial cell passage for antigen and its ***,H5N1 split vaccine or adenovirus expressed Ebola membrane protein vaccine(Ad-GPZ) were respectively immunized into

关键词： Mucosal immunization Vaccine adjuvants HTCC hydrogel Immune response

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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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