目的:为提高非诺贝特溶解度,将非诺贝特包载于PEG_(2000)-DSPE胶束中,研究其在SD大鼠体内的口服药动学情况。方法:对非诺贝特PEG_(2000)-DSPE胶束进行表征,大鼠单剂量灌胃给予非诺贝特PEG_(2000)-DSPE胶束和非诺贝特混悬液,眼底静脉丛取...目的:为提高非诺贝特溶解度,将非诺贝特包载于PEG_(2000)-DSPE胶束中,研究其在SD大鼠体内的口服药动学情况。方法:对非诺贝特PEG_(2000)-DSPE胶束进行表征,大鼠单剂量灌胃给予非诺贝特PEG_(2000)-DSPE胶束和非诺贝特混悬液,眼底静脉丛取血,HPLC法测定血浆中非诺贝特酸含量,并用药物与统计(Drug and Statistics,DAS)软件分析处理药动学数据。结果:成功制备了非诺贝特PEG_(2000)-DSPE胶束,平均粒径为(23.40±3.62)nm,包封率和载药量分别为(97.65±3.32)%和(1.33±0.32)%。大鼠体内口服药动学结果表明非诺贝特PEG_(2000)-DSPE胶束和非诺贝特混悬液的药动学行为均符合二室模型,非诺贝特PEG20 00-DSPE胶束和非诺贝特混悬液的AUC_((0-24))分别为(61.41±5.71)μg·h·ml^(-1)和(8.49±0.66)μg·h·ml^(-1),C_(max)分别为(9.67±1.65)μg·ml^(-1)和(0.71±0.09)μg·ml^(-1)。非诺贝特PEG_(2000)-DSPE胶束的AUC_((0-24))和C_(max)相比于非诺贝特混悬液组分别提高了7倍和14倍。非诺贝特PEG_(2000)-DSPE胶束相对于原料药生物利用度为723.3%。结论:非诺贝特PEG_(2000)-DSPE胶束显著提高了非诺贝特在大鼠体内的口服吸收速度和生物利用度。PEG_(2000)-DSPE胶束作为口服药物载体具有优良的应用前景。展开更多
Aim To improve the stability and optimize the tissue distribution of Evans blue liposome in rats, some surfactants such as DSPE-PEG, Tween80, and Brij35 were used to modify the Evans blue liposome. Methods The Evans b...Aim To improve the stability and optimize the tissue distribution of Evans blue liposome in rats, some surfactants such as DSPE-PEG, Tween80, and Brij35 were used to modify the Evans blue liposome. Methods The Evans blue liposome was prepared by the reverse-phase-evaporation method. The effect of cholesterol on the encapsulation percentage of Evans blue was studied. The effects of DSPE-PEG, Tween80, and Brij35 on the encapsulation percentage and tissue distribution of Evans blue liposome in the rat were determined. Results The top encapsulation percentage of Evans blue liposome is 25.30%. After modification by DSPE-PEG, Tween80, and Brij35, the encapsulation percentages decreased slightly, but not significantly. After modification, the Evans blue concentrations deceased in the liver, spleen, lung and kidney, but increased in the brain, especially in the EB-L-Tween80 group. Conclusion DSPE-PEG, Tween80, and Brij35 have slight effect on the encapsulation percentage of Evans blue liposome. The effect of Brij35 on the distribution of Evans blue liposome is similar to that of DSPE-PEG because they both is prevent the reticuloendothelial system (RES) from clearing liposome. The Evans blue concentration in the brain is greatly improved when Tween80 is used to modify the EB liposome, which is good information for preparing liposome targeting the brain.展开更多
Multidrug resistance （MDR） operated by P-glycoprotein （P-gp） is one of the major causes in the treatment failure of cancers. In this work, docetaxel-loaded mixed micelles comprised of 1,2-distearoyl-sn-glycero-3-p...Multidrug resistance （MDR） operated by P-glycoprotein （P-gp） is one of the major causes in the treatment failure of cancers. In this work, docetaxel-loaded mixed micelles comprised of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy （polyethylene-glycol）2000 （DSPE-PEG2000）, D-α-Tocopherylpolyethylene glycol 1000 succinate （TPGSIooo） and DSPE-PEG2000-folate were developed to overcome MDR and reduce the side effect of docetaxel in cancer therapy. The diameters of micelles ranged from 13 to 26 nm and the encapsulation efficiencies were all above 85%. The influences of DSPE-PEG2000 and TPGSIooo ratios on the micellar characteristics and anti-resistant tumors effects were evaluated. Micelles with high TPGS1000 amount showed an increased cellular uptake and stronger cytotoxicity against MDR KBv cells. Moreover, the micelles modified by targeting ligand of folic acid exhibited better antitumor effect on folate receptor over-expressing KBv cells. The study provides a method for overcoming MDR in cancer therapy.展开更多
目的建立EMR-Lipid dSPE结合气相色谱-串联质谱法(gas chromatography-tandem mass spectrometry,GC-MS/MS)同时测定玉米油中218种农药残留的分析方法。方法样品采用乙腈提取并经冷冻离心初次除油后用EMR-Lipid dSPE分散固相萃取净化,...目的建立EMR-Lipid dSPE结合气相色谱-串联质谱法(gas chromatography-tandem mass spectrometry,GC-MS/MS)同时测定玉米油中218种农药残留的分析方法。方法样品采用乙腈提取并经冷冻离心初次除油后用EMR-Lipid dSPE分散固相萃取净化,气相色谱-质谱联用仪多反应监测(multiple reaction monitoring,MRM)模式检测,采用基质匹配标准溶液内标法定量。结果218种农药在5~200 ng/mL范围内线性关系良好,相关系数均大于0.995,在0.05、0.10、0.50 mg/kg 3个添加水平的回收率为63.3%~119.9%,相对标准偏差(relative standard deviations,RSDs)为0.78%~18.10%,定量限(limits of the quantitation,LOQs)为10~20μg/kg。结论该方法前处理简单、高效,灵敏度、准确度和精密度高,能满足玉米油中218种农药多残留的分析要求。展开更多
为建立以HPLC-ELSD法测定顺铂脂质体中DSPE-PEG2000含量的方法,以Waters Sun Fire prep Silica(250 mm×4.6 mm,5μm)为分离柱(柱温25℃),甲醇-冰醋酸-三乙胺(500∶8∶2,V/V/V)为流动相(流速1 m L/min),蒸发光散射检测器检测(雾化温...为建立以HPLC-ELSD法测定顺铂脂质体中DSPE-PEG2000含量的方法,以Waters Sun Fire prep Silica(250 mm×4.6 mm,5μm)为分离柱(柱温25℃),甲醇-冰醋酸-三乙胺(500∶8∶2,V/V/V)为流动相(流速1 m L/min),蒸发光散射检测器检测(雾化温度50℃,蒸发温度100℃,气体流速1.6 m L/min).结果表明,DSPE-PEG2000在21.08421.6μg/m L浓度范围内线性关系良好(r=0.999 3),加样回收率为99.03%101.23%(RSD=1.08%,n=9).该法能简便、快速、准确地测定顺铂脂质体中DSPE-PEG2000含量,重复性良好.展开更多
Currently,the combination of photothermal therapy（PTT） and photodynamic therapy（PDT） has emerged as a powerful technique for cancer treatment.However,most examples of combined PTT and PDT reported use multi-compon...Currently,the combination of photothermal therapy（PTT） and photodynamic therapy（PDT） has emerged as a powerful technique for cancer treatment.However,most examples of combined PTT and PDT reported use multi-component nanocomposites under excitation of separate wavelength,resulting in complex treatment process.In this work,a novel theranostic nanoplatform（SiNcOH-DSPE-PEG（NH2）NPs） has been successfully developed by coating silicon 2,3-naphthalocyanine dihydroxide（SiNcOH）with DSPE-PEG and DSPE-PEG-NH2 for photoacoustic（PA） imaging-guided PTT and PDT tumor ablation for the first time.The as-prepared single-agent SiNcOH-DSPE-PEG（NH2） NPs not only have good water solubility and biocompatibility,but also exhibit high photothermal conversion efficiency and singlet oxygen generation capability upon 808 nm NIR laser irradiation.In addition,owing to their high absorption at NIR region,the SiNcOH-DSPE-PEG（NH2） NPs can also be employed as an effective diagnostic nanoagent for photoacoustic（PA） imaging.In vitro and in vivo experimental results clearly indicated that the simultaneously combined PTT and PDT under the guidance of PA imaging with single NIR laser excitation can effectively kill cancer cells or eradicate tumor tissues.Taking facile synthesis and high efficiency in cancer treatment by SiNcOH-DSPE-PEG（NH2） NPs into consideration,our study provides a promising strategy to realize molecular imaging-guided combination therapy.展开更多
Endotoxin detection is an important step in drug characterization. Herein we found that a chemotherapeutic drug nanoformulation composed of irinotecan hydrochloride(CPT-11) and an amphiphilic molecule DSPE-mPEG_(2000)...Endotoxin detection is an important step in drug characterization. Herein we found that a chemotherapeutic drug nanoformulation composed of irinotecan hydrochloride(CPT-11) and an amphiphilic molecule DSPE-mPEG_(2000) can interfere with the limulus amebocyte lysate assay(LAL). Furthermore, the rabbit pyrogen test(RPT) results indicated that at a relatively high dosage, the drug irinotecan hydrochloride can induce a hypothermia effect which may render the RPT results ambiguous in determination of the safety of the drug formulation.Our findings demonstrate limitations of endotoxin detection in micellar drugs,and call for the necessity of developing reliable endotoxin detection methods that can overcome the interference of nanomaterials in order to better ensure the drug safety of patients in future pharmaceutical drug development.展开更多
文摘目的:为提高非诺贝特溶解度,将非诺贝特包载于PEG_(2000)-DSPE胶束中,研究其在SD大鼠体内的口服药动学情况。方法:对非诺贝特PEG_(2000)-DSPE胶束进行表征,大鼠单剂量灌胃给予非诺贝特PEG_(2000)-DSPE胶束和非诺贝特混悬液,眼底静脉丛取血,HPLC法测定血浆中非诺贝特酸含量,并用药物与统计(Drug and Statistics,DAS)软件分析处理药动学数据。结果:成功制备了非诺贝特PEG_(2000)-DSPE胶束,平均粒径为(23.40±3.62)nm,包封率和载药量分别为(97.65±3.32)%和(1.33±0.32)%。大鼠体内口服药动学结果表明非诺贝特PEG_(2000)-DSPE胶束和非诺贝特混悬液的药动学行为均符合二室模型,非诺贝特PEG20 00-DSPE胶束和非诺贝特混悬液的AUC_((0-24))分别为(61.41±5.71)μg·h·ml^(-1)和(8.49±0.66)μg·h·ml^(-1),C_(max)分别为(9.67±1.65)μg·ml^(-1)和(0.71±0.09)μg·ml^(-1)。非诺贝特PEG_(2000)-DSPE胶束的AUC_((0-24))和C_(max)相比于非诺贝特混悬液组分别提高了7倍和14倍。非诺贝特PEG_(2000)-DSPE胶束相对于原料药生物利用度为723.3%。结论:非诺贝特PEG_(2000)-DSPE胶束显著提高了非诺贝特在大鼠体内的口服吸收速度和生物利用度。PEG_(2000)-DSPE胶束作为口服药物载体具有优良的应用前景。
文摘Aim To improve the stability and optimize the tissue distribution of Evans blue liposome in rats, some surfactants such as DSPE-PEG, Tween80, and Brij35 were used to modify the Evans blue liposome. Methods The Evans blue liposome was prepared by the reverse-phase-evaporation method. The effect of cholesterol on the encapsulation percentage of Evans blue was studied. The effects of DSPE-PEG, Tween80, and Brij35 on the encapsulation percentage and tissue distribution of Evans blue liposome in the rat were determined. Results The top encapsulation percentage of Evans blue liposome is 25.30%. After modification by DSPE-PEG, Tween80, and Brij35, the encapsulation percentages decreased slightly, but not significantly. After modification, the Evans blue concentrations deceased in the liver, spleen, lung and kidney, but increased in the brain, especially in the EB-L-Tween80 group. Conclusion DSPE-PEG, Tween80, and Brij35 have slight effect on the encapsulation percentage of Evans blue liposome. The effect of Brij35 on the distribution of Evans blue liposome is similar to that of DSPE-PEG because they both is prevent the reticuloendothelial system (RES) from clearing liposome. The Evans blue concentration in the brain is greatly improved when Tween80 is used to modify the EB liposome, which is good information for preparing liposome targeting the brain.
基金National Natural Science Foundation of China(Grant No.81273454 and 81473156)Beijing National Science Foundation(Grant No.7132113)+1 种基金National Key Basic Research Program(Grant No.2013CB932501)Doctoral Foundation of the Ministry of Education(Grant No.20130001110055)
文摘Multidrug resistance （MDR） operated by P-glycoprotein （P-gp） is one of the major causes in the treatment failure of cancers. In this work, docetaxel-loaded mixed micelles comprised of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy （polyethylene-glycol）2000 （DSPE-PEG2000）, D-α-Tocopherylpolyethylene glycol 1000 succinate （TPGSIooo） and DSPE-PEG2000-folate were developed to overcome MDR and reduce the side effect of docetaxel in cancer therapy. The diameters of micelles ranged from 13 to 26 nm and the encapsulation efficiencies were all above 85%. The influences of DSPE-PEG2000 and TPGSIooo ratios on the micellar characteristics and anti-resistant tumors effects were evaluated. Micelles with high TPGS1000 amount showed an increased cellular uptake and stronger cytotoxicity against MDR KBv cells. Moreover, the micelles modified by targeting ligand of folic acid exhibited better antitumor effect on folate receptor over-expressing KBv cells. The study provides a method for overcoming MDR in cancer therapy.
文摘目的建立EMR-Lipid dSPE结合气相色谱-串联质谱法(gas chromatography-tandem mass spectrometry,GC-MS/MS)同时测定玉米油中218种农药残留的分析方法。方法样品采用乙腈提取并经冷冻离心初次除油后用EMR-Lipid dSPE分散固相萃取净化,气相色谱-质谱联用仪多反应监测(multiple reaction monitoring,MRM)模式检测,采用基质匹配标准溶液内标法定量。结果218种农药在5~200 ng/mL范围内线性关系良好,相关系数均大于0.995,在0.05、0.10、0.50 mg/kg 3个添加水平的回收率为63.3%~119.9%,相对标准偏差(relative standard deviations,RSDs)为0.78%~18.10%,定量限(limits of the quantitation,LOQs)为10~20μg/kg。结论该方法前处理简单、高效,灵敏度、准确度和精密度高,能满足玉米油中218种农药多残留的分析要求。
文摘为建立以HPLC-ELSD法测定顺铂脂质体中DSPE-PEG2000含量的方法,以Waters Sun Fire prep Silica(250 mm×4.6 mm,5μm)为分离柱(柱温25℃),甲醇-冰醋酸-三乙胺(500∶8∶2,V/V/V)为流动相(流速1 m L/min),蒸发光散射检测器检测(雾化温度50℃,蒸发温度100℃,气体流速1.6 m L/min).结果表明,DSPE-PEG2000在21.08421.6μg/m L浓度范围内线性关系良好(r=0.999 3),加样回收率为99.03%101.23%(RSD=1.08%,n=9).该法能简便、快速、准确地测定顺铂脂质体中DSPE-PEG2000含量,重复性良好.
基金supported by the National Natural Science Foundation of China(No.21101131)National Basic Research Foundation(973)of China(No.2014CB932004)Natural Science Foundation of Fujian Province(No.2016J01073)
文摘Currently,the combination of photothermal therapy（PTT） and photodynamic therapy（PDT） has emerged as a powerful technique for cancer treatment.However,most examples of combined PTT and PDT reported use multi-component nanocomposites under excitation of separate wavelength,resulting in complex treatment process.In this work,a novel theranostic nanoplatform（SiNcOH-DSPE-PEG（NH2）NPs） has been successfully developed by coating silicon 2,3-naphthalocyanine dihydroxide（SiNcOH）with DSPE-PEG and DSPE-PEG-NH2 for photoacoustic（PA） imaging-guided PTT and PDT tumor ablation for the first time.The as-prepared single-agent SiNcOH-DSPE-PEG（NH2） NPs not only have good water solubility and biocompatibility,but also exhibit high photothermal conversion efficiency and singlet oxygen generation capability upon 808 nm NIR laser irradiation.In addition,owing to their high absorption at NIR region,the SiNcOH-DSPE-PEG（NH2） NPs can also be employed as an effective diagnostic nanoagent for photoacoustic（PA） imaging.In vitro and in vivo experimental results clearly indicated that the simultaneously combined PTT and PDT under the guidance of PA imaging with single NIR laser excitation can effectively kill cancer cells or eradicate tumor tissues.Taking facile synthesis and high efficiency in cancer treatment by SiNcOH-DSPE-PEG（NH2） NPs into consideration,our study provides a promising strategy to realize molecular imaging-guided combination therapy.
基金supported by the National Natural Science Foundation of China [Grant No. 31600812]Strategic Priority Research Program of the Chinese Academy of Sciences [Grant No. XDA09030301]+1 种基金Natural Science Foundation Key Project [Grant No. 31630027, 31430031]the National Distinguished Young Scholars Grant [Grant No. 31225009]
文摘Endotoxin detection is an important step in drug characterization. Herein we found that a chemotherapeutic drug nanoformulation composed of irinotecan hydrochloride(CPT-11) and an amphiphilic molecule DSPE-mPEG_(2000) can interfere with the limulus amebocyte lysate assay(LAL). Furthermore, the rabbit pyrogen test(RPT) results indicated that at a relatively high dosage, the drug irinotecan hydrochloride can induce a hypothermia effect which may render the RPT results ambiguous in determination of the safety of the drug formulation.Our findings demonstrate limitations of endotoxin detection in micellar drugs,and call for the necessity of developing reliable endotoxin detection methods that can overcome the interference of nanomaterials in order to better ensure the drug safety of patients in future pharmaceutical drug development.
