pH敏感阿霉素纳米脂质体的制备及性能

以阿霉素为模型药物,采用薄膜分散-pH 梯度法制备羧甲基壳聚糖修饰的纳米脂质体,并研究了该纳米脂质体的包封率、形态、粒径、稳定性和 pH 敏感性.结果表明:羧甲基壳聚糖修饰后阿霉素脂质体的ζ电位、酸性条件下药物渗漏速率、渗漏百分率比未修饰的阿霉素脂质体均有明显提高.所制pH敏感阿霉素纳米脂质体包封率达87%左右,体积粒径为(74.7±11.5)am;4℃冷藏保存3个月稳定性良好.     

羧甲基壳聚糖修饰阿霉素纳米脂质体的制备及体外细胞实验

以羧甲基壳聚糖(CMCT)为修饰剂,采用薄膜-pH梯度法制备具有pH敏感性的阿霉素纳米脂质体(CMCT-DOX-NL),以增加抗癌药物在肿瘤部位的蓄积,同时增强抗癌药物向肿瘤细胞内的传递。结果表明:制备的CMCT-DOX-NL粒子形貌圆整,粒径分布均匀为(38±22.1)nm,药物包封率为88.83%;相比传统的阿霉素纳米脂质体(DOX-NL),CMCT-DOX-NL与Hela细胞的结合和摄取均有所提高,对细胞的杀伤作用更强;CMCT-DOX-NL的体外药物释放具有明显的pH敏感性,比普通的阿霉素脂质体更能促进阿霉素(DOX)向肿瘤细胞内的传递。     

包载盐酸阿霉素的明胶-泊洛沙姆脂质体制备与表征

采用W/W型明胶-泊洛沙姆乳液体系结合二次冻干技术制备包载盐酸阿霉素的明胶-泊洛沙姆纳米脂质体。采用Sephadex G-50凝胶柱结合高压液相法建立盐酸阿霉素纳米脂质体的主药含量测定方法。通过溶液外观、粒径、Zeta电位、包封率的测定,表征盐酸阿霉素纳米脂质体的各项性能。结果表明,制备的盐酸阿霉素纳米脂质体呈现良好的圆整形态,颗粒不聚集,平均粒径为(187.02±9.56)nm,盐酸阿霉素纳米脂质体表面Zeta电位为-(16.8±1.43)mV,包封率达到(86.3±2.3)%。W/W型乳液体系结合二次冻干技术有利于制备高质量的盐酸阿霉素纳米脂质体。     

吉非罗齐纳米脂质体的制备及降脂功效的研究

制备吉非罗齐纳米脂质体并对其进行质量评价,研究其体外缓释和体内降脂作用.方法:建立吉非罗齐HPLC体外分析方法测定含量.通过乙醇注入法制备吉非罗齐纳米脂质体,考察脂质体理化性质.进行体外溶出实验检验吉非罗齐脂质体的缓释效果,小鼠体内实验检验降脂功效.结果:制得脂质体外观呈淡蓝色乳光,无沉淀,透射电镜图显示其呈类球状,分布均匀.最优处方包封率为(80.73±1.65)％,粒径为(122.82±3.61)nm,PDI为0.181±0.01,Zeta电位(-23.77±0.60)mV.吉非罗齐纳米脂质体体外24h累积释放量达到90.45％.在药效学实验中,吉非罗齐高剂量组降脂效果最好,各血浆指数均有显著变化.结论:乙醇注入法制备吉非罗齐纳米脂质体操作易行,包封率高、粒径小而均一、稳定性强,释放缓慢无突释,降血脂效果显著,为后期吉非罗齐新剂型的设计提供依据.     

壳聚糖修饰甜菜红素脂质体的制备与抗肿瘤活性

甜菜红素是一种水溶性的食品色素,具有多种良好的生物活性,但其稳定性较低,在光照、高pH、高温、酶和氧气存在的情况下容易发生降解,同时甜菜红素的生物利用度较低,不易被人体吸收.本研究制备了壳聚糖修饰的甜菜红素纳米脂质体,以提高甜菜红素的稳定性和生物利用度.采用逆相蒸发法制备甜菜红素纳米脂质体(NLP).通过测定粒径、电位...     

Box-Behnken Design-响应面优化法优化PEG化和厚朴酚长循环纳米脂质体处方

采用薄膜-超声分散法制备和厚朴酚长循环纳米脂质体,以包封率为评价指标,考察药脂比(质量比)、磷脂与胆固醇质量比例和m PEG2000-DSPE浓度3个因素对指标的影响,并对各个因素进行二次回归拟合,通过Box-Behnken Design-响应面优化法(BBD-RSM)优选最佳处方.最终优选的处方为和厚朴酚与脂类质量比为1∶20,大豆磷脂与胆固醇质量比为6.71∶1,DSPE-PEG2000浓度为13.38%,药物的平均包封率为92.32%.优化后的处方所制备的脂质体的Zeta电位稳定、粒径分布均匀,Box-Behnken Design-响应面优化法应用简便、预测性好,制备的和厚朴酚长循环纳米脂质体符合设计要求.     

K6H2［CoW11TiO40］纳米脂质体复合物的制备及性质研究

制备了包封多酸化合物K6H2[CoW11TiO40] (缩写为CoW11Ti)的纳米脂质体复合物,对其物理化学性质、包封率和含药量、粒度粒径、体外释药量及其体外抗肿瘤活性进行了研究.实验表明,多酸纳米脂质体复合物包封率为45%,含药量为23%,粒径分布在62.2～76.7nm范围内,平均粒径为69.4nm.在4℃可以稳定存在3个月.多酸化合物被包封于纳米脂质体后,活性明显高于原多酸化合物.     

表面活性剂对PLA-NPs稳定性和体外释药的影响

采用自乳化溶剂挥发法制备了不同性质表面活性剂修饰的聚乳酸纳米粒(PLA-NPs),测定其粒径和zeta电位变化,比较了不同性质表面活性剂修饰的PLA-NPs的稳定性;以5-氨基荧光素(5-AF)为模型药物,研究了4种不同性质表面活性剂修饰的PLA-NPs在pH值为7.4磷酸盐缓冲溶液(PBS)中的药物释放行为.结果表明:PLA-NPs的稳定性与表面活性剂性质密切相关;SDS,Poloxamer 188和BSA修饰的PLA-NPs具有相似的体外药物释放规律,其药物释放曲线呈现明显突释效应;CTAB修饰的PLA-NPs则呈缓慢持续释放,且药物释放量与时间呈线性关系.表面活性剂性质对PLA-NPs稳定性和体外药物释放行为均产生影响.     

鞣花酸柔性纳米脂质体的制备工艺优化与体外透皮实验

以包封率为指标,考察鞣花酸柔性纳米脂质体(EA-FNL)的最佳制备工艺,验证其透皮效果.采用薄膜分散法制备鞣花酸柔性纳米脂质体,采用高效液相色谱法检测鞣花酸柔性纳米脂质体的包封率,通过单因素实验考察表面活性剂的种类、卵磷脂与表面活性剂的质量比、卵磷脂与胆固醇的质量比、药物质量浓度、水化时间对包封率和粒径的影响.经Box-Behnken效应面法得到最优处方,测定其粒径,以大鼠腹部皮肤为材料,进行24 h透皮扩散实验.结果表明:在Box-Behnken响应面优化处方实验确定的最佳工艺中,卵磷脂与胆固醇的质量比为7.83∶1,脂质体制备水化时间为2.1 h,卵磷脂与吐温-20的质量比为2∶1,平均包封率为75.66%,粒径为(178.60±4.59)nm,聚合物分散性指数(PDI)为0.15±0.01,电位为(-30.60±0.92)mV,EA-FNL稳定性良好;EA-FNL 24 h累积透过量为9.54 μg·cm^-2,24 h后皮肤滞留量为13.77 μg·cm^-2;文中方法制备的鞣花酸柔性纳米脂质体包封率较高,粒径可控,在皮肤滞留量较高.     

MD膜驱剂对油藏矿物ζ电位的影响

用微电泳法考察了3种季铵盐(MD膜驱剂、四乙基溴化铵((Et)4NB)、十六烷基三甲基溴化铵(CTAB))和无机盐对石英砂和大庆油砂界面电性的影响.结果表明,3种季铵盐对石英砂ζ电位影响的顺序为:CTAB>MD膜驱剂>(Et)4NB.无机盐使石英砂在MD膜驱剂溶液中的ζ电位升高,无机盐中的Al3+离子影响比Ca2+和Na+离子明显.大庆油砂在MD膜驱剂和(Et)4NB溶液中的ζ电位较沥青质-大庆油砂的低,而大庆油砂在吸附沥青质前后在CTAB溶液中的ζ电位变化很小.理论计算表明,沥青质-大庆油砂饱和吸附季铵盐的ζ电位大于大庆油砂,季铵盐在沥青质-大庆油砂表面的相对覆盖率小于大庆油砂.     

基于单层MoS2纳米片的复合物制备及其光热性能和体外药物释放

将聚乙二醇(SH-PEG)修饰在单层MoS 2纳米片表面并进一步接枝聚乙烯亚胺(PEI),用以连接透明质酸(HA),从而构建一种新的HA-PEI-LA-MoS 2-SH-PEG纳米药物递送系统。用透射电镜、傅里叶变换红外光谱仪、紫外可见分光光度计、Zeta电位分析仪、动态光散射仪等仪器表征材料的形貌及理化性质。使用盐酸阿霉素(DOX)作为模型药物,研究复合物HA-PEI-LA-MoS 2-SH-PEG@DOX的体外药物释放行为。同时,在二硫化钼纳米复合物上负载一种新型的光热剂黑色素(Mel),研究其体外光热效果。结果表明:制备的纳米复合材料HA-PEI-LA-MoS 2-SH-PEG@(DOX/Mel)具有pH和近红外光(NIR)双重刺激响应药物释放的性能;黑色素的加载显著提高了MoS 2纳米复合物的光热效果,具有应用于肿瘤化学光热协同治疗的前景。     

可降解纳米氧化钇空心球载药体系的体外抗肿瘤效应

纳米氧化钇空心球在生物医学领域具有广泛的应用.以酚醛树脂微球为模板,合成出了尺寸均一、分散性好的纳米Y₂O₃空心球(HYNPs).它不仅在体外表现出显著的酸性降解行为,而且负载抗肿瘤药物阿霉素(DOX)后,载药体系HYNPs-DOX也表现出明显的pH响应药物释放特点.pH为5.0时,72 h的药物释放可达到70.46%;而pH为 7.4时,72 h的药物释放仅25.04%.进一步通过激光共聚焦显微镜监测载药体系在细胞内的DOX释放,发现随着时间的延长,细胞内DOX的荧光逐渐增加,表明DOX在细胞内释放量的增加.体外抗肿瘤细胞毒性结果显示,HYNPs对肿瘤细胞MCF-7和MDA-MB-231的活性没有影响,而HYNPs-DOX则表现出较高的体外抗肿瘤效应,与游离DOX相当.可见,该材料作为抗肿瘤药物载体具有潜在的应用价值.     

Preparation of folateconjugated starch nanoparticles and its application to tumor-targeted drug delivery vector

The lower toxicity and high effect of drug are very important for clinic therapy. So more and more atten-tion has been paid to the targeted drug delivery system. Folate receptor (FR) has been reported to be vastly overexpressed in most human tumors but se…     

Novel PLGGE graft polymeric micelles for doxorubicin delivery

Novel poly{(lactic acid)-co-[(glycolic acid)-alt-(L-glutamic acid)]}-g-monomethyl poly(ethylene glycol) (PLGGE) micelles were prepared and used as carriers for anti-tumor drug delivery. Three PEGylated PLGG copolymers (PLGGE2000, PLGGE1100 and PLGGE500) were characterized by XRD, TG and DSC. The critical micelle concentrations (CMCs) of the amphiphilic copolymers were 1.04, 0.55 and 0.13 μg/mL, respectively. The TEM, AFM and DLS measurements revealed that the micelles were homogeneous spherical nanoparticles with the diameters ranged from 50 to 150 nm when THF was used as solvent in the preparation of the micelles. Interestingly, extended cylindrical micelles were obtained using CHCl 3 as solvent. The micelles could trap doxorubicin (DOX) in the core with the highest drug loading content up to 23.7%. The mean diameter of drug loaded micelles was much bigger than that of blank micelles. The in vitro drug release of the micelles was diffusion-controlled release within the first 36 h and initial burst release was not obvious. However, after 36 h, the release rate in pH 5.0 was faster than that in pH 7.4 due to the degradation. The PLGGE micelles were nontoxic to both NIH 3T3 fibroblasts and HepG2 cells. The in vitro cytotoxicity against HepG2 cells demonstrated that the drug loaded micelles exhibited high inhibition activity to cancer cells. CLSM observation of HepG2 cells showed that DOX released from the micelles could be delivered into cell cytoplasm and cell nuclei. PLGGE micelles are potential promising carriers for anti-tumor drug delivery.     

Synthesis of pH-responsive supramolecular polypeptide nanoparticles from α-amino acids for combined chemo-photothermal therapy

A new smart supramolecular polypeptide copolymer P(Glu-co-Lys) was synthesized by the polymerization of α-amino acids using the N-thiocarboxylic acid anhydride (NTA) method, using the pH dynamic response peptide of L-glutamic acid and L-lysine as a carrier for tumor cells. The drug delivery system activated by external acid can self-assemble (pH 7.4) and disassemble (pH 5.5) under the adjustment of pH to load the drug and control its release. Doxycycline (DOX) and the photothermal reagent hydrophilic quanternary stereo-cyanine (HQS-Cy) were loaded into the peptide copolymer to obtain HQS-Cy/DOX nanoparticles (NPs) for chemo-photothermal therapy. Gentle photothermal heating can enhance the absorption of drugs by cells and enhance the efficacy of chemotherapy. In addition, chemo-photothermal therapy can solve the defect of easy recurrence after single photothermal therapy. The ingenious nanodrug delivery system of HQS-Cy/DOX NPs provides great potential for the improvement of chemo-photothermal therapy and will achieve excellent therapeutic effects in cancer treatment.     

Dialdehyde starch nanoparticles： Preparation and application in drub carrier

Dialdehyde starch nanoparticles (DASNP) were prepared by the redox reaction of NaIO4 and starch in water-in-oil microemulsion. IR spectrum showed that DASNP had aldehyde groups, and quantitative alkali consumption showed that its dialdehyde content was about (50±5)%. The average diameter of DASNP determined by SEM was about 100 nm. TGA-DTA showed that its thermal stability was better than starch nanoparticle (StNP) and dialdehyde starch (DAS). Its low biological toxicity was detected by cell experiment. Also the best mass ratio of doxorubicin (DOX) to combined DASNP detected by UV-VIS was 15 : 1, and the product was effective for controlled release of DOX. The cell experiment showed that the drug-carrier particle (DOX-DASNP) can release DOX for a long time and strengthened the effect of the anticancer drug. This work demonstrates that the DASNP, which has good thermal stability, small particle size, low biological toxicity, and slowly anticancer drug-releasing to strengthen drug effect, is a potentially useful carrier for anticancer drug.     

PLGA基载药复合微球的制备及其释放性能

以聚乳酸-羟基乙酸(PLGA)为载体材料,牛血清蛋白(BSA)为蛋白模型药物,采用复相乳化溶剂法制备PLGA载药微球,探索载药微球制备过程中囊芯比、初乳水油比、分散剂浓度、超声乳化时间对微球粒径大小、载药率、包封率的影响。结果表明,最优载药微球的制备条件为:囊芯比1:1,初乳水油比3:5,分散剂质量分数0.5%,超声乳化时间2 min。在此条件下,所得PLGA微球的粒径为268.7 nm,载药率30.88%,包封率46.95%; 电镜照片表明微球表面连续光滑,粒径分布较均匀。采用静电吸附法用阳离子聚电解质壳聚糖对最佳条件下的PLGA载药微球进行表面修饰,扫描电镜表明复合后微球粒径变大,能谱分析表明复合后微球中有N元素存在,即复合微球中存在壳聚糖,电荷测试表明微球表面带正电; 体外释放实验表明PLGA-CS复合载药微球的缓释时间延长,释药初期的突释性明显改善。     

以胶体粒子为模板制备含磁药物胶囊

以低度交联的单分散三聚氰胺甲醛(M F)微球作为胶体模板,采用层层静电自组装技术,交替组装带正电的聚二烯丙基二甲基氯化铵(PDDA)和带负电的聚4-苯乙烯磺酸钠(PSS),得到具有核壳结构的复合微球,然后利用盐酸溶液将模板M F微球溶解,制得均匀的空腔胶囊。在N aC l浓度为0.7 m o l/L,pH<3时,将抗癌药物盐酸多柔米星(DOX)和磁流体同时封装到聚电解质胶囊中,可得到含磁药物胶囊,磁性粒子分散在胶囊的壳层和空腔内。该含磁药物胶囊具有良好的磁响应性和药物缓释性。