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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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Construction and anti-tumor mechanism of novel polymeric micelles for targeted intracellular drug delivery based on hyaluronic acid and GSH-response

Construction and anti-tumor mechanism of novel polymeric mic...

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： Shaoping Yin Jue Huai Juan Li Department of Pharmaceutics China Pharmaceutical University

Objective:The aim of our study is to devebp novel polymeric micelles to achieve specific tumor targeting and rapid intracellular drug release at targetMethods:By covalently attaching stearic acid(CI8) to hyaluronic acid(HA) via a linker containing disulfide bond,HA-ss-C18 was *** copolymer HA-C18 was also synthesized for comparison Paclitaxel(PTX) was efficiently baded into *** uptake and intracellular distribution of coumarin-6loaded micelles against B16F10 cells were quantified by flow cytometry and visualized by confocal laser scanning microscopy(CLSM).NIRF imaging was employed to investigate the tumor targeting *** pharmacodynamics of drug loaded micelles were evaluated using subcutaneous tumor bearing ***:The chemical structure of HA-ss-C18 was confirmed by 1H NMR(Fig.1A).Drug loaded HA-ss-C18 micelles presented a redox triggered degradation and drug-release *** fluorescence intensity of HA-ss-C18 micelles was 2.12 folds of that of HA-C18 micelles,indicating that HA-ss-C18 micelles could be well uptaken by *** bright green fluorescence in cytoplasm indicated successful cellular uptake and great release of drugs(Fig.1B).HA receptor competitive inhibition test confirmed that HA-SS-C18 internalized into tumor cells via receptor-mediated *** assay revealed that PTX toaded HA-ss-C18 micelles showed much higher cytotoxic potency than PTX solution and PTX loaded HA-C18(p<0.05).In real-time images,the fluorescence signals in tumors of HA-ss-C18 groups were significant stronger than that of HA-C18 ***,drug toaded HA-ss-C18 showed the strongest tumor inhibition ability(p<0.05) with a tumor inhibition rate(TIR) of 70.97±7.82%.Conclusion:We provided a promising redox-responsive polymeric micelles system for targeted intracellular drug delivery and it will have a tremendous potential in cancer therapy.

关键词： polymeric micelle redox-responsive active tumor targeting HA receptor pharmacodynamics biodistribution

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Incorporation of lapatinib into human serum albumin nanoparticles with enhanced water solubility and anti-tumor effect in breast cancer

Incorporation of lapatinib into human serum albumin nanopart...

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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： Xu Wan Xiaoyao Zheng Xiaoying Pang Qizhi Zhang Department of Pharmaceutics School of PharmacyFudan University Key Laboratory of Smart Drug Delivery(Fudan University) Ministry of Education

Purpose:Lapatinib,a dual tyrosine inhibitor of EGFR and HER2,could effectively inhibit the proliferation of HER2 positive breast cancer ***,its poor water solubility restricted its clinical *** made of human serum albumin(HSA) represent promising strategy for improving water solubility of drugs and targeted drug delivery to tumor cells without any serious side ***,lapatinib-loaded HSA nanoparticles(LTNPs) were prepared and the in vitro and in vivo characteristics of the nanoparticle system were evaluated in this ***:LTNPs were prepared by Nab *** nanoparticles' morphology,structure,particle size and the drug encapsulation efficiency were ***,Coumarin-6 was used as a fluorescent probe to evaluate the cellar uptake of *** in vitro cytotoxicity of LTNPs on SKBr3 cells(HER2 overexpressing) and 4T1cells(EGFR overexpressing) were determined by MTT *** penetration and growth inhibitive effects of LTNPs were further evaluated using three-dimensional 4T1 carcinoma *** in vivo distribution of LTNPs in 4T1 tumor-bearing ICR mice was examined using LC/MS/***:HSA nanoparticles markedly elevated the water solubility of lapatinib from 7ng/ml to over 30 mg/*** were mostly spherical with a core-shell structure(Fig.l),and lapatinib was molecularly incorporated in HSA nanoparticles(Fig.2).Its mean diameters were 137.2±20.4 nmand the encapsulation efficiency was 84.9±2.45%.The uptake behavior of LTNPs by 4T1 cells presented a concentration and time-dependent manner(Fig.3).Incorporation of lapatinib in LTNPs did not decrease the cytotoxicity on both breast cancer cells compared with lapatinib solution(LTS,Fig.4).The half maximal inhibitory concentrations(IC50) of LTS and LTNP on SKBr3 cells and 4T1 cells were 9.058 ng/ml and 5.316 ng/ml,6.695 ng/ml and 5.048 ng/ml,*** favored lapatinib penetrating into the carcinoma spheroids and consequently induced more severe inh

关键词： Lapatinib HSA nanoparticles breast cancer

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A Novel Core-Shell Structural Phospholipid-Functionalized Mesoporous Silica Nanoparticles Modified with Angiopep-2 as Targeting Drug Delivery System for Brain Glioma

A Novel Core-Shell Structural Phospholipid-Functionalized Me...

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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： Wang Guowei Guo Manman Xu Junjun Zhang Rongrong Li Fanzhu Zhejiang Chinese Medical University College of Pharmaceutical Science

In order to improve the drug loading coefficient and realize the tagerted delivey of paclitaxel(PTX) to brain glioma,a novel core-shell structural phospholipid-functionalized Mesoporous Silica Nanoparticles(MSN) modified with Angk>pep-2(Ang-MSN-LP) were successfully developed using selfassembly and film hydration *** synthesized by modified-Stober method have ultrahigh surface area with remarkablely high loding ***-2 can specially combine to the bw density lipoprotein receptor-related protein(LRP) receptor overexpressed on the blood-brain barrier(BBB) and brain glioma cells,which can help to overcome the limitations of bw transport of chemotherapeutics across the BBB and poor penetration into tumor *** introducing the innovative preparation process of saturated solution adsorption method,PTX was highly encapsulated(drug loading coefficient up to 11.17%) into MSN by forming crystal anatague complex inside the *** vitro release of PTX solution,MSN-PTX,MSN-LP-PTX and Ang-MSN-LP-PTX in pH 7.4 PBS containing 20%ethanol showed that about 81.5%of PTX released from Ang-MSN-LP-PTX after 50 h and burst release was effectively reduced compared with MSN-PTX,indicating pronounced sustained-release *** bblogical safety of Ang-MSN-LP was evaluated by HBMEC and C6 cell cytotoxicity,which proved Ang-MSN-LP was good bbcompatibility and low *** cooperative targeting to brain glioma by Ang-MSN-LP was evaluated by transwell assay of HBMEC mimicking BBB models,what's more,the anti-ghoma effect of Ang-MSN-LP-PTX was assessed by C6 cell cytotoxicity and median survival time of glioma bearing rats,which showed a better anti-glioma effect than other groups that demonstrated the combinatbn of MSN-LP and angbpep-2 constituted an ideal targetingdrug delivery ***,in vivo pharmacokinetics in rats after tail vein injectbn by using blood and intracerebral microdialysis simultaneously proved that the AUCO-t in brain of Ang-MSN-L

关键词： Mesoporous silica nanoparticles Angiopep-2 Saturated solution adsorption method Blood-brain barrier Brain glioma Blood and intracerebral microdialysis simultaneously

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Synthesis,preparation and potential drug carrier of multifunctional targeted nano-carrier drug delivery system based on CD44 receptor and tumor microenvironment pH condition

Synthesis,preparation and potential drug carrier of multifun...

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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： Daquan Chen Kaoxiang Sun Youxin Li Wanhui Liu Fenghua Fu School of Pharmacy Yantai University State Key Laboratory of Long-acting and Targeting Drug Delivery System

Many studies about HA and its derivatives were reported,which can be devided into two *** type was HA-drug conjugates,also called prodrugs,the other type was the micro/nanop articles loading the different *** has been reported that both of the two types of HA can obtain some enhanced tumor targeting and therapeutic ***,some new idea was presented that the native high molecular weight hyaluronan(nHA) and oligosaccharides of hyaluronan(oHA) provoke distinct biological effects upon binding to *** has been reported that nHA binding to CD44 selectively induces CD44 clustering,which could be inhibited by oHA,which is very important and interesting for the future use of HA in drug *** irritated by highly generated HA,CD44 clustering is a unique character which can influence cell *** to the "Coating Saccharide"(CD44 clustering) of tumor surface and the slightly acidic condition of tumor,it is difficult to target the chemotherapeutic drugs to the tumor site and achieve satisfying effect for targeting *** solve this problem,we design a multifunctional oHA-histidine-ketal menthone 1,2-glycerol ketal(oHM)nano-drug delivery system with CD44 receptor as *** shown in the following figure,once oHM nanoparticles meet the CD44 receptor,the coating of CD44 clustering will not *** to the protonation of histidine imidazole group,it is useful for the cellular *** endocytosis,oHM nanoparticles will release the encapsuled drugs under the slightly acidic condition of tumor rapidly with the degration of micellar hydrophobic ketal *** encapsuled drugs will escape from lysosome to cytoplasm with good stability,produce efficacy and reduce side *** synthesis,characterization,and anti-tumor efficacy of oHM nanoparticles(oHMN)were under investigation.

关键词： pH-sensitive oligosaccharides of hyaluronan(oHA) nanoparticles drug delivery

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In situ thermo-sensitive gel with multitarget anticancer functions:an effective alternative strategy to clinical administration for remaining high efficacy and reducing toxicity

In situ thermo-sensitive gel with multitarget anticancer fun...

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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： Hongxiang Hu Zhiqiang Lin Bing He Hua Zhang Qiang Zhang Skate Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking University

Nowadays combining chemotherapeutic drug Paclitaxel(injected) with Lapatinib(oral),a tyrosine kinase inhibitor,has already been used as an effective therapy against breast cancer overexpressing HER2(Human Epidermal Growth Factor Receptor 2).In addition to improved antitumor effect,toxicity generated mainly from systematic administration of the two drugs is another aspect people concern ***,we use in situ thermo-sensitive hydrogel,F127,as a local delivery carrier incorporating Paclitaxel and Lapatinib to substitute for clinical administration with the purpose of decreasing toxicity and maintaining effect *** order to achieve stable and sustained release of drugs,we adopted strategy to incorporate PTX-NCs(Paclitaxel nanocrystals) and LAPA-MCs(lapatinib microcrystals) into the geL To investigate the effect of combination therapeuty,we chose three different kinds of cells(MCF-7/P-gp- HER2-,BT474/P-gp- HER2+,MCF-7-ADR/P-gp+ HER2+) to test their combined *** we found that the two drugs worked most effective in MCF-7-ADR and poorest in MCF-7,which meant the combined activity was likely connected with overexpression of P-gp and *** result corresponded with the previous investigation about *** also demonstrated that the phenomenon may be connected with cellular *** BT474 tumor-bearing mice as an animal model,we injected the gel containing two drugs(PTX-LAPA-gel) into the surrounding of tumors to observe its antitumor efficacy and toxicity with controls of PTX-gel,LAPA-gel and PTX-gel-LAPA-oraL As predicated,PTX-LAPA-gel was almost as effective as PTX-gel-LAPA-oral and obviously superior to other *** can also draw this conclusion from the result of induced apoptosis and anti-angiogenesis of these ***,PTX-LAPA-gel revealed less toxicity than PTX-gel-LAPA-oral because of its little drug distributing to other organs,which was demonstrated by analyzing the distribution of the two kinds of administratio

关键词： PTX MCF In situ thermo-sensitive gel with multitarget anticancer functions:an effective alternative strategy to clinical administration

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Hyaluronic acid based nanoparticle incorporating dichloro(1,2-diaminocyclohexane) platinum(Ⅱ) for tumor-targeted drug delivery

Hyaluronic acid based nanoparticle incorporating dichloro(1,...

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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： Lin Kang Xiuquan Quan Zhonggao Gao State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College Affiliated Hospital of Yanbian University

Background cis-dichlorodiammineplatinum(Ⅱ)(cis-platin,CDDP),a widely used anticancer drug,shows acute dose-related side ***(1,2-diaminocyclohexane) platinum(II)(DACHPt),a CDDP analogue,has shown lower toxicity than CDDP and no cross-resistance with CDDP in many CDDP-resistant ***,the solubility of DACHPt in water is much lower than CDDP(0.25 mg/ml for DACHPt vs.1.2 mg/ml for CDDP).Recently,many drug delivery systems have been developed to enhancing water solubility of DACHPt[l].Hyaluronic acid(HA) is a naturally occurring nonsulfated glycosaminoglycan polysaccharide with multiple biological activities and excellent biocompatibilty and biodegradability,HA and its derivatives have been popularly used as temporal scaffolds for tissue engineering and drug delivery devices for therapeutic agents[2].Objective In this study,we explored the potential possibility of methoxy polyethylene glycol(mPEG) modified HA as a biocompatible,biodegradable,and non-cytotoxic material for delivery of *** and Results Novel nanoparticle entrapping DACHPt was prepared through the polymer-metal complex formation between DACHPt and mPEG-HA in distilled water after converting DACHPt to its aqueous complex by pretreatment with AgN03(Fig.1).The mPEG modified degree of HA was determined by IH-NMR measurement(Fig.2).Subsequently,the physical and chemical properties of DACHPt/NP were *** average diameter of the nanoparticle was44.75nm(PDI=0.298).Moreover,the in vitro cytotoxicity against human non-small-cell lung carcinoma(A549) cells was ***,the targeting ability and therapeutic efficiency was confirmed by systemically injected DACHPt/NP against a experimental model of lung *** DACHPt-loaded nanoparticle showed small enough to achieve extended blood *** in vitro cytotoxicity assay against the A549 cell line showed a low IC50 value to expect high therapeutic ***,in vivo cytotoxicity against lung

关键词： Hyaluronic acid based nanoparticle incorporating dichloro diaminocyclohexane for tumor-targeted drug delivery platinum

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Novel 4-Arm-PEG-TPGS Amphiphilic Copolymer Micelles Loading Paclitaxel:Preparation,Characterization,and Evaluation

Novel 4-Arm-PEG-TPGS Amphiphilic Copolymer Micelles Loading ...

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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： Yupei Wu Songwei Tan Xiangting Zhuang Yuling Bao Tingting Wu Zhiping Zhang Tongji School of Phamarcy Tongji Medical CollegeHuazhong University of Science &Technology

Over the past few decades,the exploitation of branched PEG modified biocompatible and biodegradable polymers has received considerable *** polymers containing both hydrophobic and hydrophilic segments are of particular interest for biomedical applications,such as drug *** this study,new amphiphilic block copolymers,4-arm poly(ethylene glycol)-block-tocopheryl polyethylene glycol succinate(4-arm-PEG-C-C-TPGS、 4-arm-PEG-S-S-TPGS) with different molecular weight of 4-arm-PEG(5K、10K、20K) were synthesized to as potential paclitaxel(PTX) *** obtained copolymers were characterized by 1H NMR and gel permeation chromatography(GPC).Both the results indicated that TPGS was successfully grafted onto 4-arm-PEG with the CMC value of about 10-2 mg/*** were loaed into the micelles by a solid dispersion *** drug loading content and encapsulation efficiency of the micelles were 11.96%and 71.80%for4-arm-PEG5k-TPGS,which was much higher than that of 4-arm-PEG10k-TPGS(4.88%and 32.53%) and 4-arm-PEG20k-TPGS(5.29%and 35.27%).TEM showed that the micelles were spherical with a hydrodynamic diameter of about 200 *** PTX-loaded 4-arm-PEG5k-TPGS micelles were stable and the diameter remained unchanged more than 72 h both in PBS and fetal bovine serum(37oC).The IC50 value of the PTX-loaded 4-arm-PEG5k-C-C-TPGS micelles against A2780、A549、MCF-7were much lower than the one of *** was also found out that PTX-loaded4-arm-PEG5k-C-C-TPGS micelles did much better than PTX in vivo antitumor activity.

关键词： 4-Arm-PEG-TPGS paclitaxel micelle

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Synthesis and characterization of low-density lipoprotein modified poly-N-succinyl chitosan lipoic acid and its micelles

Synthesis and characterization of low-density lipoprotein mo...

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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： Shu-di Yang Xue-nong Zhang Department of Pharmaceutics College of Pharmaceutical ScienceSoochow University

Objective:In this paper,we report on reduction and pH dual-sensitive reversibly core-cross linked micelles based on N-succinyl chitosan lipoic acid micelles(NSC-LA.) and which are modified with LDL(LDL-NSC-LA).Paclitaxel(PTX) was used as a model drug,NSC-LA and LDL-NSC-LA as carriers,and MCF-7,a common human breast cancer cell line,as a cell model to explore the effects and preliminary mechanisms of Taxol and it's micelles in inhibiting breast cancel cells' ***:(1) LDL was isolated from human plasma by density gradient ultracentrifugation adjusted with *** and characters of Paclitaxel(PTX)were investigated.(2)NSC-LA and LDL-NSC-LA polymeric micelles was synthesized and characterized by FT-IR,1H-NMR and Raman,*** preparation was prepared by prepare LDL-coupled micelles(PTX/LDL-NSC-LA) via mild condensation *** the release behavior of polymeric micelles was determined in different release media in vitro.(3) The MCF-7 cell model in vitro was *** assay was used to determine the cytotoxicity in vitro of Taxol,two kinds of Taxol modified micelles and LDL loaded blank ***:LDL was isolated from fresh human plasma by sequential density gradient ultracentrifugation with a size distribution of(23.6±0.86)*** find the dialysis method is the best way to prepare the drug loaded *** ratio of LA was 10.11%and CMC was7.07xlO-3mg/*** mean particle size of PTX/LDL-NSC-LA was(172.0±5.5)nm,The mean particle size of polymeric micelles was(2.3±0.6)nm after adding DTT for 8.5 hours,zeta potential was(-22.57±0.40) mV;Encapsulation was 93.9%and the Drug foading of NSC-LA was 14.4%.The in vitro release studies showed that PTX release from NSC-LA micelles at pH7.4 and 37℃ was significantly inhibited by crosslinking(*** than 30%release in 72 h).The release of PTX was,however,almost doubled under endosomal pH of *** particular,rapid PTX release was observed under a reductive condition containing 10 mM glutath

关键词： Paclitaxel Low-density lipoprotein N-succinyl chitosan lipoic acid polymeric micelles reduction-Sensitive pH-Sensitive Intracellular Drug Release

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Arsenic trioxide-loaded pH-responsive mesoporous silica nanoparticles:preparation,in vitro release and pharmacokinetic studies in rats

Arsenic trioxide-loaded pH-responsive mesoporous silica 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： Manman Guo Guowei Wang Jiani Guan Junjun Xu Fanzhu Li Zhejiang Chinese Medical University College of Pharmaceutical Science

Objective To prepare arsenic trioxide-loaded pH-responsive mesoporous silica nanoparticles（PAA-ATO-MSNs） and investigate their physicochemical properties,release behavior in vitro and pharmacokinetics in rats,in order to achieve pH-responsive and sustained release of PAA-MSNs as carrier for *** PAA was covalently attached to the exterior surface of amino group functionalized MSNs prepared by sol gel *** electron microscope（TEM）,small angle X-ray diffraction（XRD）,nitrogen adsorption,and laser particle size analyzer were used to determine the physicochemical *** Entrapment efficiency（EE） and drug loading（DL） of PAA-ATO-MSNs were investigated with the method of high speed centrifugation combined with inductively coupled plasma emission spectrum（ICP）.The drug release behavior of PAA-ATO-MSNs was studied using dynamic dialysis method,PBS（pH 5.8,7.4,and 9.0） chosen as release *** ATO-Sol as control,the pharmacokinetic behavior of PAA-ATO-MSNs after intravenous injection in rats were *** concentration of ATO was determined by inductively coupled plasma mass spectrometry（ICP-MS）.Results Morphology of MSNs was spherical with obvious mesoporous *** area of MSNs was 572.2783 m2-g-1 and the pore size was 2.56 *** obvious diffraction peak occurred between 2-3°.The mean particle size,Zeta potential,EE and DL of PAA-ATO-MSNs were（148.6±0.30） nm,（-27.83±0.34） mV,（40.95±3.21）%,（11.42±1.75）%,*** vitro release behavior of PAA-ATO-MSNs has pH-responsive *** main pharmacokinetic parameters of ATO-Sol group and PAA-ATO-MSNs group were as follows:Tl/2a were（39.35 ±8.50） and（29.03±4.63） min,T1/2β were（1940.86 ±14.20） and（6381.5±35.67） min,AUC0→∞ were（3080.47±18.83） and（9069.86±21.36）μg·min·mL,AUC0→twere（706.72±9.17） and（1122.55±31.40） μg·min·mL,CL were（0.25±0.03） and（0.033±0.004） L·h·1,*** PAA-ATO-MSNs were successfully prepared with well-distributed particle size,high entr

关键词： arsenic trioxide PAA-MSNs in vitro release pharmacokinetic

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In vitro permeation characteristics of ropinirole through bovine nasal mucosa

In vitro permeation characteristics of ropinirole through bo...

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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： Yanxia Yang Weilin Gou Haitao Sun Luqin Si Gao Li Jiangeng Huang Department of Pharmaceutics School of PharmacyTongji Medical CollegeHuazhong University of Science and Technology

Objective:The aim of this study was to investigate the in vitro permeation of ropinirole,an anti-Parkinson drug,across bovine nasal ***:The permeation of ropinirole across bovine nasal mucosa was determined using Vertical Diffusion *** vitro experiments were conducted to assess the effect of directionality,donor concentration and various absorption enhancers including p-cycbdextrin(β-CD),Hydroxypropyl-p-cyclodextrin(HP-P-CD),dimethyl-P-cyclodextrin(DM-β-CD) and chitosan(CS) on the permeation of ropinirole across excised bovine nasal ***(200 u,L) were withdrawn from the receiver chamber at predetermined time intervals up to 120 min and analyzed using a validated HPLC-UV *** analysis was also performed to observe the potential irritation or toxicity of ropinirole to nasal mucosa by in vitro toad palate mucosa ***:As shown in Fig.1,the Jm-s(mucosal-submucosal flux) and Js-m(submucosal-mucosal flux) of ropinirole across the olfactory mucosa at pH 6.5 were linearly dependent upon the donor concentration range from 2 to 200 mM without any evidence of saturable ***,no significant difference was found between the Jm-s and Js-m at donor concentrations tested except 20 and 50 mM(Fig.2).Efflux transports such as P-gp might play a role in the submucosal-mucosal flux of ropinirole across the olfactory ***,no significant increase of drug permeation through the mucosa using 0.5%P-CD,1.5%HP-p-CD,1.5%DM-p-CD and 1.5%CS as absorption promoters was observed(Fig.3;Table 1).Interestingly,the permeation coefficient was found to be higher in olfactory mucosa than respiratory mucosa *** sections of the mucosa after 2 h exposure in ropinirole and saline(negative control) were similar in tissue architecture without any structure alteration,while the histological structure significantly changed after the treatment with sodium deoxycholate(positive control),indicating that ropinirole did no

关键词： ropinirole nasal delivery bovine nasal mucosa toad palate mucosa

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