抗癫疒间肽纳米粒的制备及体外释药性能的研究

目的制备抗癫疒间肽纳米粒,并研究其体外释药性能。方法选用聚乙二醇-聚乳酸-聚乙醇酸嵌段共聚物为载体,采用复乳-溶剂挥发法制备抗癫疒间肽纳米粒,以包封率、载药量等指标优化制备工艺,并研究纳米粒体外释药性能。结果抗癫疒间肽纳米粒外观呈圆形或类圆形,平均粒径为(100.2±2.45)nm,包封率和载药量分别为(64.46±1.34)%和(4.73±0.32)%,体外释药呈现缓释和突释两个阶段,符合Weibull方程。结论建立的制备工艺简便可行,得到的抗癫疒间肽纳米粒包封率和载药量较高,粒径小,体外释药具有明显的缓释特征。     

盐酸吉西他滨壳聚糖纳米粒的制备及其体外释药特性研究

目的:优化盐酸吉西他滨壳聚糖纳米粒的制备参数,考察纳米粒体外释药特性。方法:以壳聚糖为辅料,采用离子交联法制备盐酸吉西他滨壳聚糖纳米粒,以包封率、载药量、粒径为参考指标设计试验,确定优化制备参数,以透射电镜观察其表观特征,考察纳米粒体外释药程度。结果:以优化参数制备的盐酸吉西他滨壳聚糖纳米粒包封率为(78.93±1.52)%,载药量为(11.71±0.88)%,纳米粒的平均粒径为(169±24)nm,体外释放试验表明纳米粒中盐酸吉西他滨的释放过程符合Higuchi方程。结论:盐酸吉西他滨可以通过离子交联法制备壳聚糖纳米粒,其粒径、包封率、载药量可控,具有缓释效果。     

5-氟尿嘧啶纳米粒的制备及其体外释药的研究

目的以生物可降解材料乳酸/羟基乙酸共聚物(PLGA)制备5-氟尿嘧啶(5-FU)纳米粒,并考察纳米粒的体外释放特性。方法采用复乳-溶剂挥发法结合高压均质法制备5-Fu-PLGA纳米粒,用透射电镜观察纳米粒的形态,并研究了5-Fu纳米粒的粒径、载药量、包封率和体外释药。结果5-FU-PLGA纳米粒为圆整的类球形实体粒子,平均粒径为85.4nm,载药量为12.4%±0.7%,包封率为64.1%±5.3%,体外释药符合H iguch i方程:Q=0.0585t1/2 0.087(r=0.9923)。结论所制5-FU纳米粒具有明显的缓释作用。     

口服胸腺五肽乳酸-羟基乙酸共聚物纳米粒的制备及物理性质考察

目的制备供口服给药的胸腺五肽乳酸-羟基乙酸共聚物(thymopentin-poly lactic-co-glycolicacid;TP5-PLGA)纳米粒,并对纳米粒的物理性质进行考察。方法用复乳-溶剂挥发法制备TP5-PLGA纳米粒,以包封率为评价指标,用L16(45)正交设计优选纳米粒制备的处方工艺条件,用HPLC法测定胸腺五肽的含量,用激光粒度仪测定纳米粒的粒径,用透射电镜观察纳米粒的形态,用动态透析法考察纳米粒的体外释药特征。结果正交设计确定纳米粒制备的最优处方工艺条件为胸腺五肽质量浓度50 g.L-1,载体材料PLGA质量浓度100 g.L-1,乳化剂PVA质量浓度20 g.L-1;优化处方与工艺制备的纳米粒为规整的圆球形,平均粒径为(150.3±9.6)nm,载药量与包封率分别为(2.403±0.066)%与(28.12±0.60)%;体外释药结果表明,前5 h药物释放(31.27±1.5)%,存在一定突释,4 d累积释药量为(43.60±2.3)%。结论以乳酸-羟基乙酸共聚物为载体材料制备胸腺五肽纳米粒工艺简便,制剂具有良好的物理性质和体外释药特征。     

胰岛素纳米粒温敏凝胶的制备及体外释药性能

目的:制备胰岛素壳聚糖温度敏感型原位凝胶(INS-CS-NP-TISG)并进行体外释药动学考察。方法:采用离子凝胶化法制备胰岛素壳聚糖纳米粒;均匀设计法优化其处方及制备工艺,观察形态,测定粒径、表面电位、包封率和载药量;冷法配液的方法制备温度敏感型原位凝胶,改进透析袋-恒温水浴法研究胰岛素壳聚糖纳米粒温度敏感型原位凝胶溶液的体外释药动学。结果:优化制得的纳米粒呈类球形,均匀圆整,分散性好;平均粒径为(255.3±143.5)nm,在175.2~349.6nm范围内的纳米粒子达99.4%,大小均匀,分布较窄;高效液相色谱法(HPLC)测定胰岛素壳聚糖纳米粒平均包封率和载药量分别为75.84%与58.52%;表面电位(ζ)为+32.67;在人工鼻黏液中,胰岛素壳聚糖纳米粒温度敏感型原位凝胶的体外释药符合双相动力学方程,且持续释药24h。结论:选用合适的处方制备胰岛素壳聚糖纳米粒温度敏感型原位凝胶,方法简便,药物载药量高,具有较好的生物黏附性,并有一定的缓释作用。     

载羟基喜树碱聚乳酸微球的制备与体外释药研究

目的:研究载羟基喜树碱的聚乳酸微球的制备方法并考察其体外释药性质。方法:以PLA为成膜材料,采用改良乳化-溶剂挥发法,制备载羟基喜树碱的聚乳酸微球并优化制备工艺;对载药微球进行表征;超声介导下进行载药微球的体外释药试验。结果:微球粒径在1～7μm,大小均一;羟基喜树碱浓度在10mg.mL-1下,载药微球包封率为62.2%,载药量为1.69%;药物体外释药符合Higuchi方程。结论:采用乳化-溶剂挥发法,以PLA为成膜材料可制得具有较高包封率的羟基喜树碱微球,有望实现降低羟基喜树碱给药量、减少不良反应,提高靶向性的目标。     

盐酸表柔比星-聚乳酸-羟基乙酸共聚物纳米粒的制备

摘要目的制备盐酸表柔比星 聚乳酸 羟基乙酸（PLGA）共聚物纳米粒,对其进行质量评价。方法采用乳化 溶剂挥发法制备盐酸表柔比星纳米粒;对主要处方因素如PLGA用量、外水相中聚山梨酯 80用量、泊洛沙姆188和聚山梨酯 80比例进行正交设计,以药物的包封率、载药量和药物利用率等为考察指标。结果采用优化后处方制得的纳米粒药物包封率为（32.6±1.2）%,载药量为（7.2±0.5）%,药物利用率为（51.6±3.4）%,纳米粒平均粒径166.6 nm,药物可持续160 h释放。结论该方法制备盐酸表柔比星纳米粒工艺简单,无需使用聚乙烯醇,药物释放缓慢。     

表面修饰的鼻用聚乳酸载药纳米粒的制备及体外性质研究

目的 研究壳聚糖盐酸盐、吐温80、聚乙二醇20000、冰片薄荷低共溶物多重修饰的茴拉西坦聚乳酸鼻腔给药脑靶向纳米粒的制备工艺,并初步评价其体外稳定性.方法 采用溶剂扩散-蒸发法制备多重修饰的载药纳米粒,筛选并优化了其处方,考察了粒径分布、Zeta电位、包封率、载药量、稳定性及体外累积释药百分率.结果 壳聚糖盐酸盐、吐温80、聚乙二醇20000三重修饰的纳米粒形态圆整,粒径分布141.5±30.4 nm,Zeta电位20.4 mV,包封率98.14％,载药量为11.57％.所制纳米粒在溶菌酶和大鼠鼻洗液中稳定,在pH7.4和pH4.0的磷酸盐缓冲液中的24 h内累计释药百分率小于88％.结论 壳聚糖盐酸盐、吐温80、聚乙二醇20000、冰片薄荷低共溶物多重修饰的载药纳米粒包封率较高,性质稳定.     

星点设计-效应面法优化羟基喜树碱/mPEG-S-S-C18纳米粒的制备工艺

目的 制备载羟基喜树碱（hydroxycamptothecin,HCPT）还原响应mPEG-S-S-C18纳米粒,采用星点设计-效应面法筛选优化制备工艺。方法 采用乳化-溶剂挥发法制备HCPT/mPEG-S-S-C18纳米粒,应用单因素法考察投药量、水相/油相体积比、超声功率以及超声时间对载药纳米粒包封率和载药量的影响。在此基础上,以包封率和载药量作为评价指标,采用Design-Expert V8.0.6软件进行星点设计,优化载药纳米粒的制备工艺。结果 优化获得的HCPT/mPEG-S-S-C18纳米粒制备工艺投药量为1.0 mg,水相/油相体积比为4.56∶1,超声功率为562.5 W。该工艺制备的载药纳米粒包封率为（58.14±1.04）%,载药量为（3.46±0.22）%,平均粒径为（322.9±9.52） nm,多分散性指数为0.195±0.05,Zeta电位为（-17.5±2.11） mV。结论 乳化-溶剂挥发法适用于制备HCPT/mPEG-S-S-C18纳米粒,星点设计-效应面法可优化获得载药纳米粒的最佳制备工艺,所得的载药纳米粒包封率和载药量较高,所建立的数学模型预测性良好。     

口服藻酸双酯钠纳米粒的制备、体外释药特性及其药效学研究

目的为了提高藻酸双酯钠(PSS)口服制剂的稳定性及其生物利用度,制备藻酸双酯钠的口服纳米粒(PSS-NP),并对其理化性质、体外释药特性及其药效学进行考察。方法采用改进的双乳化溶剂蒸发法(W1/O/W2)制备藻酸双酯钠纳米粒并设计正交试验筛选最优处方;透射电镜观察纳米粒形态;粒度及表面电位分析仪测量纳米粒的粒径及zeta电位;氧瓶燃烧法测定载药纳米粒的包封率与载药量;超速离心法考察载药纳米粒的体外释药特性;正常小鼠灌胃给药测定降血糖效果。结果与结论优化的口服藻酸双酯钠纳米粒为规则的圆球形,其粒径大小为181.8 nm,包封率为75.80%,载药量为10.83%,zeta电位为-17.3 mV;12 h内PSS-NP累积释药百分率为60.37%;PSS-NP对正常小鼠具有显著的降血糖效果。     

5-氟尿嘧啶-N-琥珀酰壳聚糖纳米粒冻干粉针制备

目的:考察5-氟尿嘧啶-N-琥珀酰壳聚糖纳米粒(5-FU-Suc-Chi/NPs)稳定性,制备纳米粒冻干粉针.方法:采用乳化溶剂挥发法制备5-FU-Suc-Chi/NPs;考察纳米粒溶液稳定性;优化纳米粒冻干粉针处方.结果:选定12%的甘露醇为5-FU-Suc-Chi/NPs的支架剂,制备纳米粒冻干粉.结论:5-FU-...     

Norcantharidin-associated galactosylated chitosan nanoparticles for hepatocyte-targeted delivery

In this study a new chitosan (CS) derivative, galactosylated chitosan (GC), was synthesized and used to prepare norcantharidin-associated GC nanoparticles (NCTD-GC NPs) by taking advantage of the ionic cross-linkage between the molecules of the anti-hepatocarcinoma medicine NCTD and of the GC as carrier. NCTD-GC NPs were obtained with average particle size of 118.68 ± 3.37 nm, entrapment efficiency of 57.92 ± 0.40%, and drug-loading amount of 10.38 ± 0.06%. Several important factors influencing the entrapment efficiency, drug-loading amount, and particle size of NCTD-GC NPs were studied. The characteristics of sustained and pH-sensitive release of NCTD from NCTD-GC NPs in vitro were studied. In addition, in vitro cellular uptake and cytotoxicity of nanoparticles to hepatoma cell lines SMMC-7721 and HepG2 were also investigated. In vitro, and compared to CS-based NCTD-CS NPs, NCTD-GC NPs demonstrated satisfactory compatibility with hepatoma cells and strong cytotoxicity against hepatocellular carcinoma cells. In vivo antitumor activity of NCTD-GC NPs was evaluated in mice bearing H22 liver tumors. NCTD-GC NPs displayed tumor inhibition effect in mice, better than either the free NCTD or the NCTD-CS NPs. As a hepatocyte-targeting carrier, GC NPs are potentially promising for clinical applications.From the Clinical EditorIn this paper, a galactosylated chitosan (GC), was synthesized and norcantharidin (NCTD)-associated galactosylated chitosan nanoparticles (NCTDGC NPs) were generated by coupling NCTD - an anti-hepatocarcinoma drug - and GC as carrier. Compared to chitosan nanoparticles, NCTD-GC-NPs demonstrated satisfactory compatibility with hepatoma cells and strong cytotoxicity against the cells.     

分子参数对5-氟尿嘧啶-N-琥珀酰壳聚糖纳米粒理化性质的影响

目的：考察5-氟尿嘧啶-N-琥珀酰壳聚糖纳米粒（5-FU-Suc-Chi/NPs）理化性质影响因素。方法：采用乳化溶剂挥发法制备5-FU-Suc-Chi/NPs并考察其理化性质的影响因素。结果：5-FU-Suc-Chi/NPs的粒径、Zeta电位、包封率及载药量的大小与N-琥珀酰壳聚糖的取代度（DS）和分子量（Mw）有关。结论：N-琥珀酰壳聚糖的分子参数是影响5-FU-Suc-Chi/NPs理化性质的重要因素。     

蓝萼甲素固体脂质纳米粒的制备及理化性质研究

目的:制备蓝萼甲素固体脂质纳米粒,并对其理化性质进行研究。方法:用乳化-溶剂挥发法制得蓝萼甲素固体脂质纳米粒,并对其粒径、形态、表面电位、包封率、体外释药性质等进行研究。结果:所得蓝萼甲素固体脂质纳米粒的粒径分布均匀,平均粒径为(190±10·3)nm,Zeta电位为—31·2mV,平均包封率为(50·45±0·804)%;药物体外释放符合Higuchi线性方程,具有显著缓释作用。结论:固体脂质纳米粒可作为蓝萼甲素新型缓释给药系统。     

N-trimethyl chitosan nanoparticle-encapsulated lactosyl-norcantharidin for liver cancer therapy with high targeting efficacy

N-Trimethyl chitosan (TMC) was synthesized and used to prepare lactosyl-norcantharidin TMC nanoparticles (Lac-NCTD-TMC-NPs) using an ionic cross-linkage process. Lac-NCTD-TMC-NPs with an average particle size of 120.6 ± 1.7 nm were obtained, with an entrapment efficiency of 69.29% ± 0.76%, and a drug-loading amount of 9.1% ± 0.07%. The release of Lac-NCTD-TMC-NPs in vitro was investigated through a dialysis method, and its sustained effect was evident. In the human liver cancer cell line HepG2, the half-maximum inhibiting concentration (IC₅₀) of TMC-encapsulated Lac-NCTD (Lac-NCTD-TMC-NPs) was only 24.2% that of free Lac-NCTD at 24 hours. Lac-NCTD induced HepG2 cell death by triggering apoptosis. In vitro cellular uptake and in vivo NIR fluorescence real-time imaging both indicated a high targeting efficacy. In comparison with Lac-NCTD and Lac-NCTD chitosan NPs (Lac-NCTD-CS-NPs ), Lac-NCTD-TMC-NPs had the strongest antitumor activity on the murine hepatocarcinoma 22 subcutaneous model.From the Clinical EditorIn this article the preparation of N-trimethyl chitosan-encapsulated lactosyl-norcantharidin nanoparticles is described that displayed efficient targeting and sustained release in a hepatocarcinoma SC murine model.     

艾塞那肽聚乳酸-羟基乙酸共聚物纳米粒的制备及其分析方法研究

目的以聚乳酸-羟基乙酸共聚物(PLGA)为载体,用乳化复乳法制备包载艾塞那肽(EX)的PLGA纳米粒(EX-PLGANPs),并对其分析方法进行研究。方法2018年10月至2019年8月,采用Box-Behnken Design(BBD)响应面分析法对纳米粒制备的处方工艺进行优化,动态光散射技术检测EX-PLGA NPs粒径和Zeta电位;通过高效液相色谱法(HPLC)测定EX-PLGANPs中艾塞那肽含量并进行方法学验证。结果制备的EX-PLGA NPs粒径为(157.2±3.1)nm,Zeta电位为(¹19.5±2.6)mV;载药量和包封率分别为(4.41±0.28)%和(73.43±0.59)%,透射电镜图显示纳米粒外观圆整,分布均匀;EX-PLGA NPs体外稳定性良好,透析袋法释放结果显示其具有缓释效果。结论制备的EX-PLGA NPs粒径分布均一,包封率和载药量高,稳定性好,艾塞那肽含量分析方法科学有效,为艾塞那肽抗糖尿病口服缓释制剂的分析和开发提供了实验基础。     

Fabrication of long-acting insulin formulation based on poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles: preparation,optimization, characterization,and in vitro evaluation

The purpose of this research was the fabrication, statistical optimization, and in vitro characterization of insulin-loaded poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanoparticles (INS-PHBV-NPs). Nanopar-ticles were successfully developed by double emulsification solvent evaporation method. The NPs were characterized for particle size, entrapment efficiency (EE%), and polydispersity index (PDI). The NPs also were characterized by scanning electron microscopy (SEM), Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and circular dichroism (CD). The optimum conditions were found to be 1.6% polyvinyl alcohol (PVA), 0.9% of PHBV, and 15?mg/ml of insulin with the aid of the Box–Behnken experimental design results. The optimized NPs showed spherical shape with particle size of 250.21?±?11.37?nm, PDI of 0.12?±?0.01, and with EE% of 90.12?±?2.10%. In vitro drug release pattern followed Korsmeyer–Peppas model and exhibited an initial burst release of 19% with extended drug release of 63.2% from optimized NPs within 27?d. In conclusion, these results suggest that INS-PHBV-NPs could be a promising candidate for designing an injectable sustained release formulation for insulin.     

复合碳酸钙空腔纳米粒的制备及性能评价

目的 制备甘草次酸/海藻酸钠修饰碳酸钙空腔纳米粒并进行体外评价。方法 以可溶性淀粉为模板剂制备中空球状碳酸钙纳米粒（CaCO3 Nps）;在非均相体系中合成了甘草次酸/海藻酸钠聚合物（GA-ALG）;并以聚合物（GA-ALG）为壳以中空结构的碳酸钙纳米粒为核,合成了壳核结构的GA-ALG-CaCO3 Nps。采用Malvern粒度分析仪测定纳米粒子的粒度分布和Zeta电位,并通过SEM对纳米粒的形态进行表征。应用荧光分光光度计评价载盐酸阿霉素（DOX）纳米粒的载药量、包封率及体外释放特征。结果 纳米粒分布均一,平均粒径为（425.4±31.1）nm,PDI为0.289,Zeta 电位为（-17.0±0.3）mV。药物的载药量为（13.06±0.51）%,包封率为（78.35±3.08）%。;体外释放结果显示,纳米粒具有一定的缓释作用。结论 GA-ALG-CaCO3 Nps作为新型的药物载体,具有良好的pH响应性,并能显著提高载药量,还具有明显的缓释效果,为新型的纳米给药系统的深入研究提供参考。     

无稳定剂修饰的汉防己甲素PLGA纳米粒制备及体外评价

目的:制备无稳定剂修饰的汉防己甲素PLGA纳米粒,研究其理化性质及细胞毒和细胞摄取特性。方法:以聚乳酸-羟基醋酸共聚物(PLGA)为载体材料,采用无稳定剂修饰的纳米沉淀法制备汉防己甲素纳米粒;通过单因素试验考察不同制备工艺对纳米粒理化性质的影响;通过载药量、包封率、累积释药量等指标考察其载药特性;采用MTT比色法检测其对人肺腺癌细胞株A549的细胞毒性;采用共聚焦显微镜技术考察其细胞摄取特性。结果:无稳定剂修饰的汉防己甲素PLGA纳米粒平均粒径169.3 nm,与有稳定剂的汉防己甲素PLGA纳米粒相比外观无明显改变。在一定范围内,随着PLGA用量的增加,纳米粒的粒径呈上升趋势;随着投药量的增加,纳米粒的载药量显著增加,包封率下降。在pH7.4的释放介质中,纳米粒释慢释药,96 h累积释药率60.44%。细胞毒试验显示,当培养时间为8 h时,汉防己甲素组的细胞毒性大于汉防己甲素纳米粒组;当培养时间延长至24 h时,汉防己甲素纳米粒组的细胞活性明显低于纯药物组;高剂量的空白纳米粒组始终表现较低的细胞毒性。激光共聚焦电镜断层扫描显示汉防己甲素纳米粒能够较好的被细胞摄取。结论:制备的无稳定剂修饰的汉防己甲素PLGA纳米粒大小均一,包封率高,体外释药表现出较好的缓释效果,易被细胞摄取,对A549细胞的增殖有明显的抑制作用。