替莫唑胺聚氰基丙烯酸正丁酯纳米粒的制备

目的:优化工艺制备替莫唑胺聚氰基丙烯酸正丁酯纳米粒(TMZ-PBCA-NP)。方法:以α-氰基丙烯酸正丁酯(BCA)为载体,采用乳化聚合法制备TMZ-PBCA-NP,并以PluronicF-68作为表面活性剂,通过考察粒径大小和包封率2个指标,在单因素实验初选的基础上,正交设计法优化处方和制备工艺。结果:制备TMZ-PBCA-NP的优化条件为反应体系pH2.5,用1%PluronicF-68作为表面活性剂,TMZ用量5 mg,BCA单体用量0.1 mL,按优化条件所制备的TMZ-PBCA-NP平均粒径(135.8±11.3)nm,多分散系数为0.19,表面电位(-24.8±2.2)mV,包封率(44.23±2.04)%,载药量(2.80±0.05)%。结论:通过优化处方和制备工艺,采用乳化聚合法可制备出TMZ-PBCA-NP,对拓展TMZ临床给药新剂型提供一定的参考。     

大蒜素聚氰基丙烯酸正丁酯纳米粒的制备工艺研究

目的：研制大蒜素聚氰基丙烯酸正丁酯纳米粒并对处方与制备工艺进行优化筛选。方法：以生物降解型聚氰基丙烯酸正丁酯为载体材料，采用乳化聚合法制备大蒜素聚氰基丙烯酸正丁酯纳米粒；以载药量、包封率、形态和粒径分布为评价指标，通过单因素试验考查、均匀设计法优化制备工艺。结果：按优化处方与制各工艺条件，制得纳米粒球形圆整、分散良好，算术平均粒径为113．4nm，粒径分布范围为11．7—146．8nm，载药量为18．57％，包封率为92．87％。结论：经优化筛选出的工艺是大蒜素聚氰基丙烯酸正丁酯纳米粒的最佳制备工艺。     

正交设计优选阿糖胞苷聚氰基丙烯酸正丁酯纳米粒制备工艺

目的:制备阿糖胞苷聚氰基丙烯酸正丁酯(Ara-C-PBCA-NP)纳米粒.方法:在单因素考察的基础上,通过正交设计优选处方和制备工艺,并对优化条件下制备的Afa-C-PBCA-NP胶体溶液进行质量评价.结果:制备的Ara-C-PBCA-NP平均粒径为56 nm,平均粒径跨度为1.226,载药量为11.77%,包封率为53.38%.结论:所制备的稳定的纳米粒给药系统,为阿糖胞苷的临床应用提供了更广阔的前景.     

聚氰基丙烯酸正丁酯纳米粒载福莫司汀的制备工艺

目的优化工艺制备福莫司汀聚氰基丙烯酸正丁酯纳米粒（FCNU-PBCA—NP）。方法以α-氰基丙烯酸正丁酯（BCA）为载体,采用乳化聚合法制备FCNU-PBCA—NP,并加以聚乙二醇20000（PEG20000）进行表面修饰,通过考察粒径和包封率两个指标,在单因素实验初选的基础上,正交设计法优化处方和制备工艺。结果制备FCNU-PBCA—NP的优化条件为BCA单体体积分数0．8％（V/V）、FCNU20mg、PEG20000浓度2．0％,按优化条件所制备的FCNU-PBCA-NP的粒径为（124．6±5．2）nm,多分散系数（PDI）范围为0．07—0．16,包封率（64．12±2．36）％,载药量（7．28±0．76）％。结论通过优化处方和制备工艺,采用乳化聚合法可制备出FCNU—PBCA—NP,对拓展FCNU临床给药新剂型提供一定的参考。     

HPLC法测定聚氰基丙烯酸正丁酯氧氟沙星纳米粒中主药的含量

目的:建立以高效液相色谱法测定聚氰基丙烯酸正丁酯氧氟沙星纳米粒中主药含量的方法。方法:色谱柱为Kromasil C18,流动相为甲醇-四氢呋喃-醋酸盐缓冲液(40∶20∶40),流速为0.5mL.min-1,柱温为25℃,检测波长为293nm。结果:氧氟沙星检测浓度在10.02～60.10μg.mL-1范围内线性关系良好(r=0.9996,n=6),平均加样回收率为99.01%(RSD=0.64%)。结论:本方法操作简便、快速、准确,可用于该制剂的质量控制。     

苦参碱聚氰基丙烯酸正丁酯纳米粒冻干粉针剂的制备及体外释放

采用乳化聚合法制备苦参碱聚氰基丙烯酸正丁酯纳米粒,以包封率为考察指标,均匀设计优化处方与工艺.所得纳米粒平均粒径为(157.4±22.4)nm,包封率为83.8%,载药量为9.4%,体外释药具有双相动力学特征.     

注射用丝裂霉素C聚氰基丙烯酸正丁酯纳米粒的制备

采用乳化聚合法新鲜制备的注射用丝裂霉素C聚氰基丙烯酸正丁酯纳米粒平均粒径为(106.8±7.2)nm,平均包封率(92.1±2.3)%,载药量(7.3±0.2)%.半数致死剂量(LD50)本品为54.3mg/kg,注射用丝裂霉素为13.6mg/kg.     

HPLC法测定丝裂霉素C聚氰基丙烯酸正丁酯纳米粒中丝裂霉素C的含量

目的:建立高效液相色谱法测定丝裂霉素 C 聚氰基丙烯酸正丁酯纳米粒(MMC-PBCA-NP)中药物含量。方法:采用C_(18)柱(4.6 mm×150 mm,5 μm),以混合磷酸盐缓冲液-乙腈(85:15)为流动相,流速为1 mL·min~(-1),紫外检测器,检测波长为365 nm。结果:丝裂霉素 C(MMC)浓度在5～250 μg·mL~(-1)范围内与峰面积呈良好的线性关系,r=0.9998;平均回收率(n=6)为98.15%。结论:本法专属性强,操作简便,结果准确。适用于 MMC-PBCA-NP 的质量控制。     

吉西他滨聚氰基丙烯酸正丁酯纳米粒对大鼠脑移植胶质瘤的影响研究

目的:考察主动脑靶向制剂1%吐温-80包衣的吉西他滨(GCTB)聚氰基丙烯酸正丁酯纳米粒(GCTB-PBCA-NP)对大鼠脑移植胶质瘤的影响。方法:用C6脑胶质瘤细胞制作大鼠恶性肿瘤模型,14d后,15只雄性SD大鼠随机分成3组,各组分别给予1%吐温-80包衣的GCTB-PBCA-NP(GCTB包衣组)、注射用盐酸GCTB(阳性对照组)和生理盐水(阴性对照组),考察各组大鼠的平均生存时间和脑组织病理形态学。结果:GCTB包衣组、阳性对照组和阴性对照组的平均生存时间分别为(25.50±2.18)、(23.70±2.28)和(21.50±2.00)d(25.50±2.18vs.21.50±2.00,P<0.05;25.50±2.18vs.23.70±2.28,P>0.05),且GCTB包衣组脑组织病理形态学与阴性对照组比较病变恶化程度更轻。结论:1%吐温-80包衣GCTB-PBCA-NP后对大鼠脑移植胶质瘤具有一定的脑靶向及延长生存时间作用。     

胰岛素聚氰基丙烯酸正丁酯纳米粒在油介质中的稳定性及其对糖尿病大鼠的降血糖作用

目的通过对胰岛素聚氰基丙烯酸正丁酯纳米粒(IPN)在油介质(含有0.5%吐温-20和5%维生素E的豆油)中的稳定性及其口服后对链脲霉素引起的糖尿病大鼠降血糖作用的研究，希望得到一种稳定而有效的胰岛素纳米粒口服制剂。方法依据IPN中的胰岛素含量，IPN的平均粒径和粒子跨度，及其体外释药来评估其稳定性。将IPN分散在含有0.5% 吐温-20，pH 2.0的水溶液中作为对照。结果研究表明，不论样品是在(25±2) ℃条件下避光放置1年，还是在体外与3种消化道酶37 ℃酶解30 min，油介质中的IPN都比水介质中IPN稳定性好。依据单剂量po给药后，在0-144 h血糖降低的百分数与时间曲线上面积(AAC)可知，po IPN的油溶液(50 u·kg^-1)相对于sc胰岛素(2 u·kg^-1)的生物利用度为22.4%，明显高于po IPN水溶液的相对生物利用度(15.5%)。结论分散在油介质中的IPN具有较好的稳定性和相对较高的生物利用度，因此，含有0.5%吐温-20和5%维生素E的豆油有望成为口服胰岛素聚氰基丙烯酸正丁酯纳米粒的有效而稳定的分散介质。     

丝裂霉素C聚氰基丙烯酸正丁酯磁性纳米球对肝细胞L-02的生长抑制作用

目的　研究丝裂霉素C聚氰基丙烯酸正丁酯磁性纳米球 (MMC PBCA MNPS)、PBCA MNPS和MF(磁流体 )以及MMC对正常人肝细胞株 (L 0 2细胞 )生长抑制作用的影响。方法　用乳化聚合法分别制备了PBCA MNPS与MMC PBCA MNPS;采用MTT比色法研究了不同浓度的MMC PBCA MNPS、PBCA MNPS、MF与MMC对L 0 2细胞生长抑制作用的影响 ;用自动生化仪测定了乳酸脱氢酶 (LDH)活性。结果收稿日期 :2 0 0 4-0 2 -0 3 ,修回日期 :2 0 0 4-0 3 -19基金项目 :国家“863”资助项目 ( 2 0 0 2AA2 14 12 1) ;广东省攻关资助项目 ( 2 0 0 2C3 0 10 3 )作者简介 :任　非 ( 1974-) ,女 ,博士 ,研究方向 :生物药剂学 ,Tel:0 2 0 6164 1888 872 3 6,E mail:renfeisky @tom .com ;陈建海 ( 1947-) ,男 ,教授 ,博士生导师 ,研究方向 :生物高分子材料 ,生物药剂学不同浓度的MMC PBCA MNPS对L 0 2细胞的相对抑制率(RIR % )为 :10 0 %、15 1%、2 5 1%、32 1%、39 9%与 4 5 0 % ;不同浓度的PBCA MNPS的RIR %依次为 :1 8%、5 2 %、10 0 %、12 9%、15 1%与 2 9 9% ;不同MMC浓度的RIR %依次为 :2 2 1%、35 1%、4 6 1%、6 2 0 %、80 1%与 88 9%。MF不仅不抑制L 0 2细胞的生长 ,还有利于细胞的生长。按照相对生长率 (RGR % ) ,MMC PBCA M     

Studies on paclitaxel-loaded glyceryl monostearate nanoparticles

Solid lipid nanoparticles (SLNs) of Paclitaxel were prepared by modified Hot homogenization method using Glyceryl monostearate (GMS). The SLNs were characterized for its physicochemical characteristics such as mean particle size, percentage entrapment efficiency and zeta potential, which were found to be 226 nm, 92.43% and ?29.4 mV, respectively. The Transmission Electron Microscopy (TEM) studies showed that prepared SLNs were of spherical shape. The drug retarding efficiency of the lipid (GMS) was better in pH 7.4 compared to pH 3.5. The release profile showed a tendency to follow Higuchi diffusion pattern at pH 7.4 and Peppas-Korsenmeyer model at pH 3.5. Chemosensitivity assay carried out using B16F10 cell lines showed that anti-proliferative activity of Paclitaxel was not hindered due to encapsulation.     

Major effects on blood-retina barrier passage by minor alterations in design of polybutylcyanoacrylate nanoparticles

Abstract

Because the blood-brain barrier (BBB) is an obstacle for drug-delivery, carrier systems such as polybutylcyanoacrylate (PBCA) nanoparticles (NPs) have been studied. Yet, little is known of how physiochemical features such as size, surfactants and surface charge influence BBB passage in vivo. We now used a rat model of in vivo imaging of the retina - which is brain tissue and can reflect the situation at the BBB - to study how size and surface charge determine NPs’ ability to cross the blood-retina barrier (BRB). Interestingly, for poloxamer 188-modified, DEAE-dextran-stabilised, fluorescent PBCA NPs, decreasing the average zeta-size from 272?nm to 172?nm by centrifugation reduced the BRB passage of the NPs substantially. Varying the zeta potential within the narrow range of 0–15?mV by adding different amounts of stabiliser revealed that 0?mV and 15?mV were less desirable than 5?mV which facilitated the BRB passage. Moreover, whether the fluorescent marker was adsorbed or incorporated also influenced the transport into the retina tissue. Thus, minor changes in design of nano-carriers can alter physicochemical parameters such as size or zeta potential, thus substantially influencing NPs’ biological distribution in vivo, possibly by interactions with blood constituents and peripheral organs.     

Exposure to silver nanoparticles induces size- and dose-dependent oxidative stress and cytotoxicity in human colon carcinoma cells

The antimicrobial properties of silver nanoparticles (AgNPs) have made these particles one of the most frequently utilized nanomaterials in consumer products; therefore, a comprehensive understanding of their toxicity is necessary. In particular, information about the cellular uptake and size dependence of AgNPs is insufficient.In this study, we evaluated the size-dependent effects of AgNPs by treating the human LoVo cell line, an intestinal epithelium model, with spherical AgNPs of well-defined sizes (10, 20, 40, 60 and 100 nm). The cellular uptake was visualized by confocal laser scanning microscopy, and various cytotoxicity parameters were analyzed in a size- and dose-dependent manner. In addition, the cellular proteomic response to 20 and 100 nm AgNPs was investigated to increase the understanding of potential mechanisms of action. Our data indicated that cellular uptake and toxicity were regulated by size; smaller particles easily penetrated the cells, and 100 nm particles did not. It was hypothesized that this size-dependent effect resulted from the stimulation of a signaling cascade that generated ROS and inflammatory markers, leading to mitochondrial dysfunction and subsequently inducing apoptosis. By contrast, the cell proliferation, was independent of AgNPs particle size, indicating a differentially regulated, ROS-independent pathway.     

齐墩果酸聚氰基丙烯酸正丁酯纳米囊在小鼠体内的肝靶向研究

目的:研究齐墩果酸聚氰基丙烯酸正丁酯纳米囊(OA-PBCA-NC)在小鼠体内的肝靶向性。方法:小鼠尾静脉注射OA-PBCA-NC试验组及齐墩果酸(OA)对照组,HPLC法测定小鼠心、肝、脾、肺、肾各脏器及血浆中OA的含量,比较两组体内分布特点,并进行靶向性评价。结果:秩和检验结果表明静脉注射OA-PBCA-NC试验组与OA对照组比较,其在肝脏的分布差异有显著性,OA-PBCA-NC静脉注射给药后能显著增加OA在肝脏的分布。试验组各肝靶向指标结果均优于对照组。结论:OA-PBCA-NC能增加OA的肝靶向性。     

聚α-氰基丙烯酸丁酯载药纳米微粒的研究进展

目的：对作为药物载体的聚α-氰基丙烯酸丁酯的研究进展进行综述，就其制备工艺、体外释药和体内分布、毒理学和稳定性等作一介绍。方法：查阅聚α-氰基丙烯酸丁酯作为载药毫微粒的国内外文献。结果：聚α-氰基丙烯酸丁酯作为药物载体具有生物利用度高、释药速率可控、靶向性，能够改变药物体内分布等优点。结论：聚α-氰基丙烯酸丁酯作为药物载体具有广阔的应用前景。