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检索条件"任意字段=2012年中国药物制剂大会——中国药学会药剂专业委员会年会、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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Peptide-modified biodegradable nanoparticles targeting the blood-brain barrier

Peptide-modified biodegradable nanoparticles targeting the b...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、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： Chi Zhang~(a,b),Qingfeng Liu~(a,b),Yong Qian~(a,b),Qizhi Zhang~(a,b*) Department of Pharmaceutics,School of Pharmacy,Fudan University,Shanghai,201203,People's Republic of China Key Laboratory of Smart Drug Delivery,Ministry of Education & PLA,PR.China,201203

Purpose To develop and evaluate a new targeting delivery system that employs PEG-PLA nanoparticles modified with a cyclic peptide CRTIGPSVC(Pep-NP)for targeting of blood-brain barrier(BBB). Methods PEG-PLA nanoparticles(NP)were prepared by the emulsion/evaporation method,and the cyclic peptide CRTIGPSVC was covalently conjugated to the surface of *** in vitro cytotoxicity of NP and Pep-NP were examined at various concentrations with BCEC cells after 4 h incubation at 37℃by MTT ***-6 was used as a fluorescent probe to evaluate the cellar uptake of nanoparticles by BCEC *** brain targeting effect was evaluated using the real-time fluorescence imaging analysis with the near infrared due DiR as a probe. Results Both NP and Pep-NP were spherical and of regular size(Fig.1).The mean diameters of the Pep-NP were increased slightly to 170.2±3.37 nm compared with 167.7±1.50 nm of the NP,both with good polydispersity index(PDI<0.25).No obvious cytotoxicity was observed in either modified or unmodified nanoparticles with the cell viability value above 90%,indicating their noncytotoxicity (Fig.2).The uptake behavior of NP and Pep-NP presented a time-dependent manner(Fig.3).The fluorescence of Pep-NP was markedly stronger than that of NP at each examined time *** the quantitative analysis(Fig.3),the value of fluorescent intensity of Pep-NP was 4085 after 2h incubation,which is 2.01 times of that of NP(2031).Optical in vivo images of nude mice were taken 1 h after the injection of DiR-loaded NP and DiR-loaded ***-NP was obviously accumulated in brain compared with NP (Fig.4A).The fluorescence signal was not notable in the brain of mice administrated with *** images of ex vivo brains also displayed stronger fluorescence intensity in mice treated with Pep-NP,indicating the brain targeting effect of the Pep-NP(Fig.4B). Conclusion:The results clearly indicated that the cyclic peptide modified nanoparticles system showed great potential in drug deliv

关键词： Blood-brain barrier(BBB) Brain delivery PLA nanoparticles Cyclic peptide

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Multifunctional arms co-mediated lipid drug delivery system for tumor-targeted therapy

Multifunctional arms co-mediated lipid drug delivery system ...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、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： Bai Xiang.Xian-Rong Qi Department of Pharmaceutics,School of Pharmaceutical Sciences,Peking University,Beijing,People's Republic of China 100191

Background:RNA interference(RNAi)has exhibited highly sequence-specific gene silencing in which short interfering RNA (siRNA)suppress the expression of genes holding sequence *** extensive research effort is under way to develop siRNAs as therapeutics for many kinds of diseases. Commonly used CPPs include TAT,polyarginine,penetratin,and *** majority of known CPPs are not cell or tissue specific,which remains the major drawback for CPP application as drug delivery *** this study,we chose polo-like kinase-1 (PLK-1)as a target and develop an activable cell-penetrating peptides(ACPPs)/Folate anchored liposome sensitive to prostate-specific antigen(PSA)/prostate-specific membrane antigen(PSMA)for prostate tumor-targeting therapy. Methods and Results:First,we synthesize the DSPE-PEG-ACPP and DSPE-PEG-Folate conjugates,*** results of MALDI-TOF MS are in agreement with the calculated mean molecular weight of the conjugates. Then,five type PLK-1 siRNA-loaded liposomes were prepared by a film-extrusion and post-insertion method:normal liposomes(3% DSPE-PEQ mol ratio,N-L),CPP liposomes(3%DSPE-PEG-CPP and 3%DSPE-PEQ mol ratio,C-L),Folate liposomes(1% DSPE-PEG-Folate and 3%DSPE-PEQ mol ratio,F-L),ACPP liposomes(3%DSPE-PEG-ACPP and 3%DSPE-PEQ mol ratio,A-L) and ACPP/Folate hybrid liposomes(1%DSPE-PEG-Folate,3%DSPE-PEG-ACPP and 3%DSPE-PEQ mol ratio,AF-L).The sizes of all these liposomes were about 180～210 nm with a small polydispersity index(<0.3).Zeta potential of liposomes,from 0 mV to 20 mV,showed that formulations,to some extent,have positive surface charges. Fluorescence activated cell sorting(FACS)and confocal laser fluorescence microscopy(CSLM)techniques were used to investigate the in vitro cellular interaction of all type liposomes with 22Rv1 prostate carcinoma ***,among these liposomes. C-L lead to the highest cell uptake of *** the activation of enzymatically active PSA,the obviously enhanced internaliza

关键词： RNA interference Cell-penetrating peptides Activable cell-penetrating peptides Polo-like kinase-1 Prostate-specific antigen Prostate-specific membrane antigen

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p-Hydroxybenzoic Acid(p-HA) Modified Polymeric Micelles for Brain-targeting drug delivery

p-Hydroxybenzoic Acid(p-HA) Modified Polymeric Micelles for ...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、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： Zhixin Zhang.Xiaoli Wei,Xiaoyu Zhang,Changyou Zhan,Weiyue Lu~* Department of Pharmaceutics,School of Pharmacy,Fudan University.Key Laboratory of Smart Drug Delivery(Fudan University),Ministry of Education & PLA,China.826 Zhangheng Road,Shanghai 201203,China.

Objective:Chemotherapy for brain diseases has been hampered due to the inability of transport of drug across the blood-brain barrier(BBB).In order to overcome the barrier,a small molecule,benzamide analogue p-hydroxybenzoic acid(p-HA),was used as a ligand for brain-targeting. Methods & Results:The p-HA was conjugated to PEG-DSPE to form ***-loaded polymeric micelles were prepared by a thin-film hydration method using methoxy-poly(ethylene glycol)-distearoylphosphatidylethanolamine (mPEG2000-DSPE)as a carrier and the p-HA-PEG-DSPE as a brain targeted *** prepared micelles showed spherical with a mean diameter of(18±3)*** efficiency and drug loading were(83.49±1.3)%、(7.7±1.2)%for unmodified micelles and(80.65±1.6)%、(7.47±1.8)%for p-HA-modified micelles,*** vitro drug release testing showed that the micelles could achieve sustained docetaxel(DTX)release.p-HA-modified micelles showed improved cellular uptake by the BCECs cells compared to the unmodified *** vivo and ex vivo near-infrared fluorescence imaging experiments demonstrated that brain targeting ability of the p-HA-modified micelles were 1.3-1.8 times higher than that of the unmodified *** vitro cytotoxicity assay against U87 MG glioblastoma cells showed that the p-HA-modified micelles loaded with DTX increased inhibition of tumor cell growth compared to that of the unmodified micelles and Taxotere?,which indicated that the anti-glioblastoma effect of DTX could be enhanced by the p-HA-modified polymeric ***-glioblastoma study in a xenograft mouse model of human glioblastoma multiforme(GBM)showed that p-HA-conjugated micelles could significantly elongate the lifetime of U87 grafted mice compared to saline,Taxotere? and mPEG-micelles groups(P<0.05). Conclusion:p-HA-modified micelles can improve the anti-gliobalstoma effect of DTX,which demonstrated that the p-HA-modified PEG-DSPE micelles are promising brain-targeted drug delivery nano

关键词： p-Hydroxybenzoic acid Docetaxel Polymeric micelles Brain targeting Anti-glioblastoma effect

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A stable and effective peptide c(LyP-l) for tumor targeted drug delivery system

A stable and effective peptide c(LyP-l) for tumor targeted d...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、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 Wang~1,Meilin Wu~1,Zhiqiang Yan~(1,2),Xiangkun Yang~1,Xiaoyu Zhang~1,Weiyue Lu~(1,*) 1 Key Laboratory of Smart Drug Delivery,Ministry of Education & PLA,Department of Pharmaceutics,School of Pharmacy,Fudan University,Shanghai 201203,PR China 2 National Engineering Research Center for Nanotechnology,Shanghai 200241,PR China

Objective:LyP-1 is a cyclic peptide that can specifically bind to tumor cells and tumor *** improve the targeting efficacy of rumor targeted drug delivery system,a new peptide c(LyP-l)was synthesized to improve the stability of the targeting ligand LyP-1. Then c(LyP-1)was conjugated to liposomes to study its tumor targeting efficacy. Methods & Results:To improve LyP-1 stability,the liner LyP-1 peptide chain was cyclized through amide linkage instead of previously disulfide bond.c(LyP-1)showed a 2 times improved stability in the presence of serum(Fig A).LyP-1-or c(LyP-1)-conjugated PEG-liposomes were prepared by the thin-film hydration and extrusion *** targeting ability of LyP-1-LS/DiR and c(LyP-l)-LS/DiR to SCI 375 human melanoma tumor xenografts was detected using an in-vivo fluorescent imaging *** compared the in vivo anti-tumor efficacy of LyP-1-LS/DOX and c(LyP-l)-LS/DOX in SCI 375 human melanoma tumor xenografts-bearing nude mice.c(LyP-1)-LS/DOX showed an enhanced rumor targeting(Fig B)and inhibiting effect (Fig C)compared with LyP-1-LS/*** immunofluorescence technique was used to evaluate the binding ability of c(LyP-1)-LS/FAM and the destroying ability of c(LyP-l)-LS/DOX to tumor *** results showed that c(LyP-l)maintained the targeting ability to tumor lymphatics(Fig D),and that c(LyP-l)-LS/DOX exhibited much higher lymphatics disruption effect than LyP-1-LS/DOX(FigE). Conclusion:These findings strongly suggest that c(LyP-l)is a stable and effective targeting ligand for tumor targeted delivery *** study presents a new approach for improvement of tumor targeted treatment.

关键词： c(LyP-1) stability liposomes(LS) doxorubicin(DOX) tumor-targeted therapy

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Preparation and Characterization of Anti-HER2 Affibody modified PE38KDEL-Ioaded PEGylated immunoliposomes

Preparation and Characterization of Anti-HER2 Affibody modif...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、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： Lei Zhang,Ying Lu,Yanqiang Zhong Department of Pharmaceutics,School of Pharmacy,Second Military Medical University,Shanghai 200433,China.

Objective:Toxin protein of immunotoxin produces a strong non-specific toxicity in the body,and greatly limits their broad clinical ***2:342-PE38KDEL-loaded anti-HER2 PEGylated liposomes(ZP-Affisomes)were constructed. Methods:Particle size and morphology of ZP-Affisomes and ZP-liposomes were observed by dynamic light-scattering detector (DLS)and transmission electron microscope(TEM).BCA assay was used to determine the drug loading,encapsulation efficiency, and high performance liquid chromatogaphy(HPLC)was used to determine ZHER2:342 conjugation efficiency on the ZP-liposomes. Recognition property,cytotoxicity against targeted cell and the antitumor mechanism of ZP-Affisomes were studied in vitro *** binding ability of ZP-Affisomes(biological activity of ZHER2:342)was demonstrated by flow cytometry(FCM). The binding and internalization of ZP-Affisomes to BT-474 cells were analyzed by laser scanning confocal microscopy(LSCM). Cytotoxicity against HER2-over expressed breast cancer BT-474 cells was analyzed using cellular cytotoxicity assays. Results:ZP-Affisomes were quiet round and homogenous with a 140～160nm average size *** had presented on the ZP-liposomes surface due to the increase in particle size(141.8nm→160.8nm).The drug loading and encapsulation efficiency of optimized prescription were 14.12±0.34μg/mg and 73.04±2.54%(n=5)respectively,and the conjugation efficiency was about 60.57±0.38%,the ZHER2:342 density was 18.17±0.12ng/*** FCM result showed ZP-Affisomes could recognize and bind to the targeted cell,the biological activities of ZHER2:342 on the liposomes were well *** binding and internalization of targeted liposomes were detected on the ZHER2:342 cell membrane after 1 h incubation by ***-Affisomes had remarkable in vitro cytotoxicity against HER2-overexpressing breast cancer BT-474 cells. Conclusion:The anti-HER2 Affibody(ZHER2:342)modified ZHER2:342-PE38KDEL PEGylated Immunoliposomes had drama

关键词： Affibody ZHER2.342-PE38KDEL PEGylated immunoliposomes Breast Cancer Cytotoxicity

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Self-assembled Methoxy Poly(ethylene glycol)-Cholesterol Micelles for Hydrophobic Drug Delivery

Self-assembled Methoxy Poly(ethylene glycol)-Cholesterol Mic...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、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： Yiyi Yu~1,Yingju He~3,Bei Xu,Zhiyao He,Ying Zhang~2,Yan Chen~1,Yang Yang~3,Yongmei Xie~1,Yu Zheng~1,Gu He~1,Xiangrong Song~(1,*) 1 State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China 2 School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products,Kunming Medical University, Kunming,Yunnan 650500,China 3 West China School of Pharmacy,Sichuan University,Chengdu,Sichuan 610041,China

Objective:to promote the application of methoxy poly（ethylene glycol）-cholesterol（mPEG-CHOL）in hydrophobic drugs loading, mPEG-CHOL was used to prepare core-shell micelles（DTX-PM）encapsulating docetaxel（DTX）with poor water solubility by modified co-solvent evaporation ***:approaches investigated for the enhancement of DTX entrapment efficiency（EE） and the minimization of particle size included the organic and aqueous phase composing,the organic/aqueous phase volume ratio and the polymer concentration（Fig.1）.The optimal DTX-PM was characterized by dynamic light scattering（DLS）,transmission electron microscopy（TEM）and differential scanning calorimetry（DSC）,besides storage stability and in vitro cytotoxicity assay. Results:DTX-PM produced by optimal formulation had higher EE（97.6%）and DL（4.76%）(Table.1)with the diameter of 13.76±0.68 nm（Fig.2）and PDI of 0.213±*** showed that the micelles were spherical（Fig.3）,and DSC analysis proved that DTX was successfully entrapped into mPEG-CHOL micelles（Fig.4）.The in vitro cytotoxicity experiments displayed that blank micelles had no effect on the growth of SKOV-3,BXPC-3,A549 and HepG-2 cells,demonstrating that mPEG-CHOL was one of biocompatible biomaterials（Fig.5）.The ICvalues of DTX-PM on SKOV-3,BXPC-3,A549 and HepG-2 cells were 10.08 ng/mL, 7.6 ng/mL,28.37 ng/mL and 125.75 ng/mL,***:DTX-PM with small particle size and uniform distribution could encapsulate docetaxel at high *** micelles had the similar antitumor activity to free DTX in vitro,indicating that mPEG-CHOL was a promising micellar vector for the hydrophobic drug *** addition,this work provided a new and facile approach to prepare drug loaded micelles with controllable performances.

关键词： Co-solvent evaporation Methoxy poly(ethylene glycol) Cholesterol Polymer Micelles Docetaxel Stability Hydrophobic drug

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Novel compound components of Danshen and Sanqi loaded PLGA nanoparticles for brain delivery via inner ear administration:In vitro and in vivo evaluation

Novel compound components of Danshen and Sanqi loaded PLGA n...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、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： ZHANG Xiao,CHEN Gang~(1,2) 1 Department of Pharmaceutics,School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006,China 2 Guangdong Provincial Key Laboratory of Advanced Drug Delivery,Guangzhou 510006,China

Objective:The main goal of this study was to develop novel compound components of Danshen and Sanqi loaded poly （D,L-lactide-co-glycolide）(PLGA)nanoparticles（NPs）and evaluate their potential in protective effects on brain injury via inner ear ***:PLGA NPs loaded with salvianolic acid B（Sal B）,tanshinoneⅡA（TSⅡA）and panax notoginsenoside （PNS）(notoginsenoside R and ginsenoside Rg,Rb)were prepared by double emulsion/solvent evaporation *** were characterized for entrapment efficiency,loading capacity,morphology,particle size,surface charge and in vitro release. Pharmacokinetics of NPs in guinea pigs were investigated following intratympanic administration（IT）and intravenous injection（Ⅳ）. The effect of NPs on cerebral ischemia reperfusion（I/R）injury in guinea pigs and the toxicity of IT assay were also performed. Results:The optimized NPs were displayed the satisfactory entrapment efficiency（91.81%for TSⅡA,92.88%for Sal B,37.87% for R,44.98%for Rg,,and 93.56%for Rb,,respectively）.The loading capacity of NPs were 0.14%for TSⅡA,2.24%for Sal B, 1.87%for R,7.32%for Rg,and 8.43%for *** copolymers formed spherical shape in a small *** mean diameter of NPs was about 154 nm with PDI 0.007 and zeta potential-44 ***,in vitro drug release behavior shown that NPs had a good sustained-release characteristics（Fig.1）.NPs following IT in guinea pigs,greatly improved drug distribution within the inner ear, CSF and brain tissues compared withⅣ（Tab.1）.Pharmacodynamics studies demonstrated that NPs following IT markedly inhibited oxidizing reactions and protected brain from cerebral ischemia reperfusion（I/R）injury by upregulating superoxide dismutase（SOD） activity both in the serum and brain tissues,simultaneously significantly reducing the levels of malondialdehyde（MDA）and nitric oxide synthase（NOS）(Fig.2-Fig.3).And intratympanic delivery did not cause injury of cochlear function by the toxicity of IT assay （Fig.4）.Conclusion:These findings sugges

关键词： PLGA nanoparticles intratympanic administration brain delivery salvianolic acid B tanshinone IIA panax notoginsenoside cerebral ischemia reperfusion injury

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Pluronic P123 micelle drug delivery system loading Itraconazole:development,evaluation and its effect on intestinal P-glycoprotein

Pluronic P123 micelle drug delivery system loading Itraconaz...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、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： Weilin Guo,Yang Hu,Jiangeng Huang,Luqin Si,Gao Li~* School of Pharmacy,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

Objective:To enhance the intestinal absorption of the itraconazole（ITZ）,a micelle drug delivery system employing Pluronic P123 was *** second aim of this study was to further investigate the role of P-glycoprotein efflux in rat intestinal absorption of itraconazole. Methods:ITZ-loaded P123 micelle was prepared by film dispersion method and the central composite design-response surface method（CCD-RSM）was utilized to optimize the *** particle size,encapsulation efficiency and drug-loading coefficient of optimal formulation were ***,the in vitro release profiles of itraconazole from P123 micelle and the conventional capsule in artificial gastric juice（pH 1.2）and artificial intestinal juice（pH 6.8）were compared using the small glass *** ITZ-loaded P123 micelle（1 mg/mL）or Sporanox? suspension（2 mg/mL）was orally administered to the rats at a 15 mg/kg itraconazole *** samples（0.5 mL）were obtained from tail vein at predetermined time *** addition,in situ single-pass intestinal perfusion was performed to investigate the correlation between itraconazole intestinal absorption and P-glycoprotein. Results:The optimal composition of the ITZ-loaded P123 micelle was:60 mg Pluronic P123,1mg ITZ,17.5 mL deionized water. The encapsulation efficiency and drug-loading coefficient were 60.23%and 1.12%,*** 1:100 dilution of itraconazole P123 micelle with deionized water,the particle size was in the range of 30-40 *** release rate of ITZ from micelle was significantly higher than that of commercial Sporanoxcapsules and was not remarkably changed with the pH value of dissolution medium（Figure 1）.The main pharmacokinetic parameters of the two formulations were shown in Table *** Cfor oral administration of ITZ-loaded P123 micelle in rats significantly increased compared with those from Sporanox ***,the micelle was also extended MRT and tof ITZ in *** results of in situ single-pas

关键词： Itraconazole Pluronic P123 micelle drug delivery system intestinal absorption P-glycoprotein

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Novel drug nanocarriers combining Chitosan,cyclodextrins and polyethylene glycol

Novel drug nanocarriers combining Chitosan,cyclodextrins and...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、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： Shanshan Gao~1,Yixing Tu~1,Fang Yao~1,Feng Gao~(1,2,3*) 1 Department of Pharmaceutics,School of Pharmacy,East China University of Science and Technology,Shanghai,200237,P.R. China.2 Shanghai Key Laboratory of Functional Materials Chemistry,East China University of Science and Technology,Shanghai, 200237,P.R.China.3 Shanghai Key Laboratory of New Drug Design,East China University of Science and Technology,Shanghai 200237,P.R.China

OBJECTIVE Important efforts and advances in biotechnology have facilitated the production of many new drugs with ideal therapeutical effect. But most candidate drug showed very low bioavailability because of their poor *** the drug delivery strategies intended to increase the solubility of drugs,the use of polymeric nanocarriers has shown a significant degree of *** objective of this study was to explore the possibility of obtaining nanoparticles composed of chitosan(CS), heptakis(2,6-di-O-methyl)-P-cyclodextrins(DM-β-CD)and polyethylene glycol(PEG).The molecular weight(Mw)of CS and PEG were investigated for the Mw of them might have a role in the drug release in some *** rationale used was to combine the drug solubilizing and stabilizing properties of DM-β-CD with the mucoadhesive properties of CS and prolonged action properties of PEG in a unique nanoparticle drug delivery *** the physicochemical properties of DM-β-CD /PEG/CS nanoparticles were characterized regard to their size,surface charge,and ***(PTX)was used as a model drug,and drug release from PTX-loaded DM-β-CD/PEG/CS nanoparticles in vitro or in vivo was further investigated. METHODS The series of CS,DM-β-CD/CS,PEG/CS and DM-β-CD/PEG/CS nanoparticles were prepared by ionic gelation using sodium tripolyphosphate(TPP)as *** particle size and zeta potential of the assemblies in aqueous solutions were performed using dynamic light scattering(DLS).Structure and morphological evaluation of DM-β-CD/PEG/CS nanoparticles was performed with Fourier Transform Infrared spectrometer(FTIR)and Transmission Electron Microscopy(TEM).Elemental Analyser and X-ray Photoelectron Spectrometry(XPS)was used to determine the composition of *** optimization formulation was definited through the single *** obtain the nanoparticles spherical and fine distributed,many single factors were investigated in our study,such as the different Mw of CS and

关键词： chitosan cyclodextrin polyethylene glycol ionic gelation nanoparticles NDDS

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Characterization and modulation of drug resistance of chemical conjugation of Methotrexate in Pluronic micelles in vitro and in vivo

Characterization and modulation of drug resistance of chemic...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、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： Yanzuo Chen~a,Jijin Gu~a,Zhuoyang Fan~a,Xianyi Sha~a,Xiaoling Fang~(a*) a Key Laboratory of Smart Drug Delivery(Fudan University),Ministry of Education & PLA,Department of Pharmaceutics,School of Pharmacy,Fudan University,Lane 826,Zhangheng Road,Shanghai 201203,China.

Multidrug resistance（MDR）in cancer is a major cause for the failure of anti-cancer chemotherapy with elevated expression of particular proteins,such as glycoprotein P（P-gp）.It was found that some Pluronics could inhibit the P-gp efflux system,resulting in drastic sensitization of these tumors with respect to anticancer agents. In the present study,we synthesized Methotrexate（MTX）conjugated Pluronic P105（P105-MTX）and used F127 as functional biomaterials to form a F127/P105-MTX mixed micelles（F127/P105-MTX）for efficient modulation of drug *** F127 with long PEO chains formed hydrophilic shell can reduce the rate of mononuclear phagocyte system *** P105,a promising triblock copolymer for sensitizing resistant tumors,which is easy to be conjugated to MTX through three steps.H-NMR spectrum was shown in *** conjugation percentage of MTX to Pluronic F127 was 95.45%on a molar ratio *** conjugation of drugs to polymers can form stable bonds,which should be relatively stable to prevent drug release during its transport before the cellular localization of the ***-film hydration method was used for prepared F127/P105-MTX *** micelle was around 160nm（Fig.2A）with theζ-potential value-2.08±0.45mV,and exhibited spherical shape of moderate uniform particle size by TEM image and AFM image（Fig.2B,C）.The drug loading rate was 5.3%.The physical status of MTX was investigated by DSC（Fig.3）.The endothermic melting peak around 167.3°C disappeared,indicating that MTX did conjugate to P105 in the polymer matrix of F127/P105-MTX.F127/P105-MTX exhibited controlled release behavior compared with free MTX（Fig.4.）, which had higher and faster release at slightly acidic condition. In vitro biocompatibility study was carried out using KB,KBv and HEK-293 cell lines,and blank micelles showed much lower cytotoxic effect than Pluronic F127 and P105,especially on non-cancerous cells HEK-293（Fig.5.）.Cytotoxic activity results showed the viabilit

关键词： Polymeric micelles Pluronic Methotrexate Multidrug resistance

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