荷载JQ1/紫杉醇PLGA纳米粒的制备

研究荷载JQ1/紫杉醇PLGA纳米粒的制备,并考察其对黑色素瘤细胞表面PD-L1表达情况的影响。采用乳化溶剂蒸发法制备荷载JQ1/紫杉醇的PLGA纳米粒,并对所制备的纳米粒进行粒径、形貌等理化性质表征;尾静脉注射荷载JQ-1/紫杉醇PLGA纳米粒后,考察大鼠体内的药动学参数;以B16黑色素瘤细胞为模型,应用流式细胞术分析PLGA纳米粒对B16细胞表面PD-L1表达情况的影响。结果表明,所制备的PLGA纳米粒平均粒径为210 nm,其外观呈光滑圆球状。大鼠体内单次静脉注射PLGA纳米粒后,呈二室模型分布,紫杉醇与JQ1主要的药动学参数如下:分布相半衰期为0.142 8、0.169 9 h,消除相半衰期为5.27、2.37 h,血药浓度曲线下面积为8.155、3.793 (μg·h)/mL,清除率为122.612、131.795 mL/(h·kg),表观分布体积为766.07、396.25 mL/kg。流式分析结果表明经PLGA纳米粒组处理后,可降低B16黑色素瘤细胞表面PD-L1的表达。表明所制备的PLGA纳米粒可作为紫杉醇与JQ1两种药物共递送的传输载体,有望提高免疫治疗肿瘤的效果。     

黄芩苷固体脂质纳米粒的制备及大鼠在体肠吸收研究

选用硬脂酸、单硬脂酸甘油酯混合脂质作为载体,以卵磷脂作为乳化剂制备黄芩苷固体脂质纳米粒(BC-SLN),并考察其大鼠在体肠吸收特性.采用热匀质法(hot homogenization technique,HHT)制备BC-SLN,采用循环灌注技术评价黄芩苷固体脂质纳米粒和黄芩苷溶液大鼠在体肠吸收特性.制得的BC-SLN平均粒径为(150.8±47.2)nm,zeta电位为(-39.85±0.86) mV,载药量为(4.86±0.37)%,包封率为(88.52±0.32)%,大鼠在体肠吸收实验表明,BC-SLN与黄芩苷溶液相比,吸收速率常数Ka和每小时吸收百分率p均呈增加趋势,有显著性差异(P＜0.05),黄芩苷固体脂质纳米粒能够促进黄芩苷大鼠肠吸收.     

丁香苦苷单体与丁香苦苷PLGA纳米粒药动学比较

测定大鼠血浆中含丁香苦苷的量,并对具有抗乙肝病毒的丁香苦苷单体和丁香苦苷PLGA纳米粒进行大鼠体内药动学比较研究.采用色谱柱:Diamonsil C18(5μm,250×4.6 mm)流动相为甲醇-水(50∶50,V/V);流速为1.0 mL/min;检测波长为221 nm;进样量为20μL.测定Wistar大鼠尾静脉注射丁香苦苷后不同时间血浆中的药物质量浓度.给药剂量相同(10 mg/mL)时,丁香苦苷PLGA溶液的T1/2α和T1/2β值是丁香苦苷溶液的1.23倍和2.25倍.AUC值是丁香苦苷溶液的3.09倍,血浆清除率约为丁香苦苷溶液的1/3.经过数据拟合发现丁香苦苷单体与丁香苦苷PLGA纳米粒在大鼠体内过程均符合二室模型,载药纳米粒给药后,使丁香苦苷能在体内较长时间维持较高的血药质量浓度,起到一定的缓释作用.     

坚龙胆不同部位中龙胆苦苷的含量比较

目的：测定坚龙胆不同部位龙胆苦苷的含量,并评价坚龙胆药材不同部位的质量。方法：采用HPLC法,色谱条件为Agilent ZORBAX SB C18色谱柱（4.6mm×150mm,5μm）,流动相为甲醇∶水（27∶73）,检测波长274nm,流速1.0ml/min,柱温25℃。结果：测定了坚龙胆药材不同部位中龙胆苦苷的含量。龙胆苦苷在0.21～10.5μg范围内线性关系良好,r值为0.999 8,龙胆苦苷平均回收率为98.01%,RSD为2.50%。结论：坚龙胆药材不同部位龙胆苦苷含量均高于《中国药典》2005年版要求,表明坚龙胆全草均可入药。     

激素类药物醋酸地塞米松纳米粒的制备及其质量评价

以单硬脂酸甘油酯为载体,应用乳化-溶剂挥发法制备醋酸地塞米松纳米粒,测定其粒径、药物包封率等性质。经过正交优化试验确定其优选方案为：载体材料单硬脂酸甘油酯的用量为0.3g,表面活性剂为硬脂酸聚烃氧酯（S-40）/泊洛沙姆（F68）（质量比为7/3）的混合物,有机相氯仿与水相的体积比为5：75,蒸发有机相氯仿时的真空度为0.05MPa。制备所得的醋酸地塞米松纳米粒球体均匀度好,平均粒径在100nm左右,载药纳米粒的包封率在89.03%左右。     

超声提取-HPLC法测定秦艽中龙胆苦苷的含量

目的 用高效液相色谱法测定秦艽样品中龙胆苦苷的含量。方法采用水提法为对比,以水、乙醇和甲醇为溶剂,用频率为20kHz的超声波提取秦艽中的龙胆苦苷,并用HPLC法测定样品中龙胆苦苷的含量,并对两种工艺的秦艽样品的主体成分龙胆苦苷进行定量比较。结果表明超声提取能够明显地提高秦艽中龙胆苦苷的浸出率。结论通过运用正交试验法,确定了秦艽的粒径大小(目数)、超声波处理时间(min)以及水剂量(mL)3个因素的最佳组合。     

正交试验法优选坚龙胆中龙胆苦苷的提取工艺

目的:优选坚龙胆中龙胆苦苷的提取工艺.方法:以龙胆苦苷的含量为指标,采用高效液相色谱法进行含量测定,采用L9(34)正交设计试验,对提取次数、提取溶剂倍数和提取时间3因素进行考察,以确定最佳提取工艺.结果:提取3次,用10倍量的甲醇,提取时间每次20min为最佳提取工艺.结论:该工艺合理,且稳定可行.     

优化提取工艺对龙胆中两种苦苷提取率的影响

考察不同提取方法对龙胆中龙胆苦苷和獐牙菜苦苷提取率的影响.采用高液相色谱分析法,比较甲醇超声提取、甲醇冷浸提取、水煎煮提取、乙醇渗漉提取四种样品制备方法对龙胆苦苷和獐牙菜苦苷提取率的影响.其中乙醇渗漉提取法对两种成分提取效率高;同时确定了最佳渗漉条件.该提取方法操作简便易行,提取效率高,可用于药材龙胆及其制剂的质量分析.     

拨云锭中龙胆苦苷的含量测定

目的:建立拨云锭中龙胆苦苷的含量测定方法。方法:采用高效液相色谱法测定拨云锭中龙胆苦苷的含量,以AgilentTC-C18(4.6 mm×150 mm,5μm)为分析柱,流动相为甲醇-水,检测波长为274 nm。结果:龙胆苦苷含量在0.219 2～2.192 0μg时,线性关系良好(r=0.999 8),平均回收率为97.6%(n=9),RSD为2.37%。结论:此方法操作简便、回收率高,重现性好,可用于本品中龙胆苦苷的含量测定。     

Preparation,characterization and release of methyl viologen from a novel nanoparticle delivery system with double shells of silica and PLGA

The use of nanotechnology in drug delivery is a rapidly expanding field. Biodegradable or nontoxic nanomaterials have the most promising application potentials in nanomedicine. Herein, we report a novel core-shell nanoparticle with double shell coatings (silica and poly(D,L-lactide-co-glycolide) (PLGA)) with the total shell thickness of (8.7 ± 1.3) nm. The outer shell of PLGA is biodegradable and used for controlled and sustained release, and the inner shell of silica is mesoporous for the preservation of t...     

Preparation and cellular uptake of PLGA particles loaded with lamivudine

Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with lamivudine and coated with bovine serum albumin (BSA) were prepared via a double emulsion method. The influences of experiments parameters such as volume of inner aqueous phase, concentration of organic phase and ultrasonication time on the particle size and drug entrapment efficiency were investigated, obtaining PLGA particles with a diameter of ~260 nm and drug entrapment efficiency of ~35%. The particles were observed by scanning electron microscopy and transmittance electron microscopy, showing a core-shell structure. BCA assay found that 58 mg BSA was present on/in 1 g LPB particles. The loaded lamivudine showed a burst release at beginning and sustained release until 24 h in physiological conditions. Low pH could accelerate the release of lamivudine from PLGA particles, making the PLGA particles potential intelligent intracellular drug carriers. The PLGA particles were readily internalized into the human liver cells within a short time and increased gradually with the prolongation of incubation time regardless of the loading of lamivudine. The particles either resided within lysosomes or transferred to cytoplasm, but could not enter into the cell nucleus. The cell viability was not significantly influenced in the presence of the particles regardless of lamivudine encapsulation, suggesting that this kind of particles may be a good candidate for the intracellular anti-hepatitis B drug delivery.     

5-氟尿嘧啶毫微粒的制备工艺

以生物可降解材料乳酸-乙醇酸共聚物为载体,采用复乳-溶剂挥发法结合高压均质法制备5-氟尿嘧啶毫微粒,通过正交试验设计优化5-氟尿嘧啶毫微粒的制备工艺,用透射电镜观察毫微粒的形态,并对所制得毫微粒的平均粒径、载药量、包封率及重现性进行了研究.实验结果表明优化制备工艺条件下所制得的5-氟尿嘧啶毫微粒为圆整的类球形实体粒子,平均粒径为85.4 nm,载药量为(12.4±0.7)%,包封率为(64.1±5.3)%,制备工艺简单,重现性好.     

Preparation,characterization and antibacterial property of naringin loaded PLGA nanospheres

Naringin is a predominant flavanone in grapefruit and shows a variety of biological effects such as antioxidative, anticancer, anti-inflammatory and antibacterial activity. However, its application in pharmaceutical field is limited by low water solubility, poor bioavailability and instability. To overcome the problem, naringin has been encapsulated in poly(lactic-co-glycolic acid) (PLGA) polymer by emulsion-diffusion-evaporation method in this work. Moreover, naringin loaded PLGA nanospheres were characterized by scanning electron microscope (SEM), dynamic light scatter method (DLS), fourier transform infrared (FTIR) spectra, UV–vis spectra and fluorescence spectra of DNA-EB competition displacement. The mean diameter of PLGA nanospheres and NRG/PLGA nanospheres was 123 ?± ?25 ?nm and 137 ?± ?30 ?nm, respectively. The drug encapsulation efficiency was 86.4% while the drug loading rate was 22.3%. The fluorescence spectra of the competitive DNA-binding experiments revealed that the functional activity of naringin was retained after loaded in PLGA. It is revealed that the initial burst effect happened in the initial 24 ?h and followed by sustained release lasting for 10 days. Moreover, the nanospheres exhibited strong antibacterial activity, and 99.9% of E. coli and S. aureus were killed when treated with naringin loaded PLGA nanospheres at the concentration of 0.2 ?mg ?mL^?1 within 24 ?h. Furthermore, the viable cells remained only 48% when the concentration of NRG/PLGA nanospheres was 32 ?μg ?mL^?1 and NRG/PLGA nanospheres was important for inhibition of cancer cells. It is concluded that the stable naringin loaded PLGA nanospheres could have potential application in food industry and nanomedicine field.     

S/O/W法制备PLGA/TiO2载药微球

将纳米TiO2吸附溶液中的BSA由水包油包固体乳化法用PLGA包裹药物粒子.通过紫外和SEM等检测手段,考察纳米TiO2在不同条件下对BSA吸附率的影响,以及不同制备工艺下PLGA包裹药物粒子对载药量和包封率及体外释放的影响.研究结果表明,当溶液的pH值接近蛋白质等电点、温度在20 ℃左右、反应24 h时,TiO2吸附BSA量最大,药物粒子分布均匀,尺寸在40 nm左右.在制备微球时,当初乳体积降低、PVA浓度降低及PLGA与药物粉末的质量比增大时,载药量和包封率都有提高,且微球体外释放较小.微球表面光滑,尺寸为4 μm左右.     

烘干温度对秦艽中龙胆苦苷含量的影响

目的检测不同烘干温度对秦艽中龙胆苦苷含量的影响。方法采用HPLC测定在不同烘干温度下干燥的秦艽品中龙胆苦苷的含量。结果在20℃,40％,60℃,80℃,100℃烘干秦艽时, 随温度升高,秦艽中龙胆苦苷的含量逐渐升高,在100℃时达到最高,其含量为8．55％。在100％℃, 120℃,140℃,160℃,180℃,200℃时,龙胆苦苷的含量逐渐下降,在200℃时含量降至最低,其含量为3．27％。结论秦艽药材最佳的烘干温度为100℃,在此温度下烘干的秦艽药材中龙胆苦苷的含量最高,且干燥时间较短。     

响应面法优化龙胆苦苷脂质体的复乳法制备工艺

采用复乳法制备脂质体,使用3因素3水平的Box-Behnken响应面设计,以脂质体的包封率、载药量和综合评价为响应值,考察龙胆苦苷药液质量浓度、第一次乳化超声时间及膜材中磷脂与胆固醇的质量比对响应值的影响,并用Design-Expert 7.1.3软件（试用版）进行数据拟合、数学建模和预测分析。优化出的龙胆苦苷脂质体的最佳处方为龙胆苦苷药液质量浓度为2.04 mg/mL、第一次乳化超声时间为7.07 min、脂质体膜材中胆固醇与磷脂质量比为0.45。研究结果表明,在最优处方下龙胆苦苷脂质体形态完整、状态稳定,平均粒径为131 nm,其包封率为52.39%,与预测值的偏差率小于1%。     

制备附载rhTGF-β1的PLGA缓释支架及其对MSCs细胞形态的影响

为探讨自制的附载转化生长因子-β1(rhTGF-β1)的D,L-乳酸-CO-乙醇酸(PLGA)体外缓释生物支架对人骨髓间充质干细胞(MSCs)细胞形态的影响,制备了附载rhTGF-β1的PLGA生物支架,并检测了在PLGA的降解过程中rhTGF-β1的释药规律;同时分离培养人骨髓间充质干细胞,体外培养后分别接种于附载和未附载rhTGF-β1的PLGA支架上.通过扫描电镜观察不同时间段MSC在支架上的生长情况,实验结果表明,rhTGF-β1能被包裹进PLGA支架中,而且可在PLGA支架降解过程中持续释放出来.通过扫描电镜还观察到实验组支架上细胞呈多角或梭形,且有较多基质分泌,而对照组细胞较少.因此附载转化生长因子-β1的PLGA复合载体是一种较为理想的新型生物支架.     

直接熔融缩聚法合成PLGA的表征及其生物相容性研究

本文旨在探究一条更加适合用于医学研究的高分子材料PLGA的合成途径。首先在无催化剂、高真空条件下直接熔融缩聚合成聚乳酸-聚乙醇酸（PLGA）的无规则共聚物,对其合成反应体系的最佳温度范围、反应时间进行确定,然后对反应产物的分子量、结构、亲水性能、热性能以及不同比例LA/GA的产物特性粘数等物化性质进行表征,对合成的高分子材料PLGA的生物相容性进行分析与讨论。结果显示在无催化剂、高真空、160~175℃、LA/GA的比例为3∶7左右、反应时间60 h左右下合成的高分子材料PLGA具有较稳定的物化性质和较好的生物相容性,可以作为以后用于医学研究的高分子材料PLGA的合成途径。