三种不同表面活性剂对羟基磷灰石纳米颗粒的表面修饰的比较

目的:本研究旨在通过不同方法修饰羟基磷灰石纳米颗粒并检测其稳定性及分散性。方法:首先采用水合热合成法制备羟基磷灰石纳米颗粒,然后用透射电镜(TEM)和场发射扫描电镜(SEM)对其表面形态结构进行表征。我们首次用溴化十六烷三甲基铵(CTAB),PEG2000和人血清对羟基磷灰石纳米颗粒通过共价结合或表面吸附的方式进行表面嫁接,并利用透射电镜,傅里叶红外光谱(FT-IR)和X射线衍射(XRD)对新合成的这三种纳米羟基磷灰石复合物的形貌,结构和晶粒粒径进行表征。对这三种羟基磷灰石纳米颗粒悬浮液的时间沉降曲线进行分析。在分散性上通过检测这三种羟基磷灰石复合物悬浮液在不同pH值下的Zeta电位并绘制Zeta-pH曲线。结果:我们发现CTAB修饰的羟基磷灰石纳米颗悬浮液的悬浮稳定性最佳,其次是PEG2000,最后是人血清。在pH=7.0时,CTAB修饰的羟基磷灰石纳米颗粒的zeta电位值是25.68 m V,而PEG2000修饰的Zeta电位是4.32m V,人血清修饰的Zeta电位是-13.23m V。结论:CTAB表面修饰的羟基磷灰石纳米颗粒相对于其它两种表面活性剂复合物具有更好的分散性和悬浮稳定性,与DNA/RNA结合能力更强。本课题的结果给羟基磷灰石纳米颗粒载体的应用提供了一种新的选择,有望利用亲和力更高的基因载体实现基因治疗,具有广阔的应用前景。     

青花椒精油纳米乳的制备及其体外抑菌活性研究

目的：研究制备青花椒精油纳米乳的最优配方,并对其理化性质和体外抑菌活性进行考察。方法：采用相转变法制备青花椒精油纳米乳并绘制伪三相图筛选其配方工艺,然后使用粒径分析仪、透射电子显微镜等对其表征形态进行检测,最后考察青花椒精油纳米乳在体外对大肠杆菌和金黄色葡萄球菌的抑制活性。结果：青花椒精油纳米乳最优配方为：12.63%蓖麻油聚氧乙烯醚（EL-40）、4.21%1,2-丙二醇、7.33%青花椒精油、75.82%蒸馏水。以此配方为基础制备的青花椒精油纳米乳整体澄清透明、流动性和稳定性均良好。试验制备的青花椒精油纳米乳平均粒径为126.1±0.78 nm,分散指数为0.591±0.21,呈正态分布;透射电镜下其形态为球形,分布均匀、分散性良好,载药量为73.29±1.56 mg/mL。体外抑菌实验表明,青花椒精油纳米乳对金黄色葡萄球菌和大肠杆菌的MIC值均为2.29 mg/ml,且青花椒精油纳米乳抑菌效果优于青花椒精油。结论：制备得到的青花椒精油纳米乳工艺简单,显著提升了青花椒精油的抑菌活性。     

川芎挥发油羟丙基-β-环糊精包合物的制备及其性能研究

制备川芎挥发油羟丙基-β-环糊精(hydroxypropyl-β-cyclodextrin, HP-β-CD)包合物,提高川芎挥发油的溶解度及稳定性。采用单相法制备包合物,以包合率为评价指标,正交试验法优选包合工艺条件。运用扫描电镜(SEM)和红外光谱(IR)进行表征,对包合物进行溶解度和稳定性考察。采用单相法制备该包合物的最优工艺条件为乙醇体积分数95%,挥发油∶HP-β-CD(W/W)=1∶10,HP-β-CD∶乙醇(W/V)=1∶3,包合率达92.34%。表征结果表明包合物已形成,HP-β-CD使川芎挥发油溶解度显著提高,包合物在60℃条件下10天稳定性良好。优选的包合工艺重现性好、包合率高,制备方法简便高效,能显著提高川芎挥发油的溶解度及稳定性。     

含不同表面活性剂的高效氟氯氰菊酯水乳剂对桃小食心虫的防治效果

【目的】在保证菊酯类农药防治桃小食心虫效果的基础上,降低乳油农药助剂和溶剂对环境的危害,开发农药新剂型。【方法】研究了含不同表面活性剂的4种2.5%高效氟氯氰菊酯水乳剂的配方、热稳定性、制剂粒度、稀释液表面张力及其在苹果叶面的接触角,并在苹果园针对桃小食心虫进行了田间防治效果试验。【结果】采用4种不同表面活性剂(FMEE、IS-TEO、宁乳34、农乳700)配比组成的4种高效氟氯氰菊酯水乳剂1号、2号、3号、4号,配方热贮后分解率低于5%,符合国标热贮稳定性的要求;粒径D50在0.85~2.12μm处于水乳剂型理想范围;稀释液表面张力43.32~51.89 m N/m;稀释液在苹果叶面接触角为47.45°~74.38°,远低于水的表面张力,均能较好的附着于苹果叶表面。4种配方稀释2 000~3 000倍液对苹果桃小食心虫的防治效果为84.62%~100%,与对照药剂4.5%高效氯氰菊酯乳油无显著差异,较乳油制剂有机溶剂用量减少70%。【结论】综合热稳定性、制剂粒径、稀释液表面张力、稀释药液在苹果叶面接触角、对苹果桃小食心虫防治效果及农药减量化使用等因素,推荐使用3号配方。     

丁酸氯维地平静脉脂肪乳剂的质量评价

目的:通过对丁酸氯维地平静脉脂肪乳各指标进行检测,对所制备的丁酸氯维地平静脉脂肪乳的质量进行评价,确保制剂的稳定、安全、有效.方法:制备静脉脂肪乳剂,通过测定制剂含量、粒径、电位、pH值、过氧化值、游离脂肪酸值、甲氧基苯胺值等指标对制剂进行质量评价.结果:丁酸氯维地平的峰面积(Y)与浓度(X)在0.1～100 μg·mL-1范围内具有良好线性关系,Y=51801X+17659,R2=0.9999(n=3),检测限为0.8ng,所制备的丁酸氯维地平静脉脂肪乳剂的平均含量为97.06％,平均粒径243.2± 2.08nm,zeta电位-36.2±0.25,pH 7.03±0.11,过氧化值0.01 mL,游离脂肪酸值0.20± 0.01,甲氧基苯胺值2.08±0.07,渗透压306±8.96 mOsmol·Kg-1.结论:所制备丁酸氯维地平脂肪乳的含量符合要求,标示含量在90.0％-110.0％的限度范围,渗透压及pH均与人体血液环境相接近,平均粒径小且分布集中,过氧化值、游离脂肪酸值及甲氧基苯胺值均较低,制备的乳剂性质稳定、重复性好,能够达到国外进口同种制剂的标准.     

载MD-CPT透明质酸纳米微乳经皮给药作用于瘢痕修复的研究

喜树碱衍生物对瘢痕疙瘩成纤维细胞的增殖有明显的抑制作用,为提高药物利用度,提供透皮给药的治疗途径,本文采用微乳法制备了一种新的O/W型透明质酸纳米载体(HA-GMS),包载药物10,11-亚甲二氧基喜树碱(MD-CPT),制备过程中无酒精,且没有使用化学增强剂,经透射电镜和激光粒度仪分别测得HA-GMS纳米乳粒径为(177.33±27.11)nm,zeta电位为-15.6±1.7,多分散系数为0.55±0.01,纳米微乳对MD-CPT药物的包封率为(77.85±1.29)%,且稳定性良好.用MTT法检测HA-GMS对人正常细胞HSF、HUVECs的作用,细胞相对存活率为75%~95%,生物相容性良好,用HA-GMS对瘢痕疙瘩成纤维细胞培养48 h,其生长抑制率为28.2%.HA-GMS纳米乳运载的MD-CPT皮肤渗透量明显高于对照组MD-CPT乙醇溶液对皮肤的渗透量,作用4 h的累积渗透量分别为(660.72±20.54)μg/cm2和(102.73±13.81)μg/cm2,HA-GMS纳米乳明显增加了MD-CPT的透皮效率,本研究结果为透皮给药治疗瘢痕疾病提供了基础.     

质粒纳米乳剂的制备与阴离子交换色谱测定方法

以纳米乳剂为载体包裹草原兔尾鼠卵透明带3DNA疫苗,制备获得了纳米乳剂DNA疫苗,并对其进行了质量评价。采用界面乳化法制备质粒纳米乳剂,用电子显微镜测定了其粒径及其分布,根据质粒的带电特性,利用强阴离子Q SepharoseTMXL色谱柱分离纳米乳剂和游离质粒,建立了强阴离子交换柱质粒纳米乳剂包封率的快速测定方法。结果表明:制备的纳米乳剂DNA疫苗的平均粒径为(23±10)nm,包封率为80.5%。选择0.05mol/L的Tris-HCl为平衡液,流速为0.7mL/min,紫外检测波长260nm,柱温30℃,进样量为2mL的实验条件,质粒的含量和峰面积的线性关系良好(r=0.9983),加样回收率在95%以上,该方法简便快速、灵敏度高,重复性好,可用于纳米乳剂DNA疫苗包封率的快速测定。     

肉桂油纳米微乳的制备

本研究采用转相乳化法,结合伪三元相图制备肉桂油纳米微乳,对其外观、类型、理化性质、粒径及微观形态进行考察。最终得到肉桂油纳米微乳由EL-40/Tween80/无水乙醇/IPP/肉桂油/水组成,所制备的肉桂油微乳为O/W型微乳,淡黄色、澄清透明、流动性好,透射电镜下微乳颗粒大小均匀,平均粒径32 nm,电导率111.0μs/cm,折光率1.415,黏度105 mpa.s,pH值5.24。     

暗黑鳃金龟对性信息素的触角电生理及行为反应

为了分离鉴定暗黑鳃金龟的性信息素成分并对其功能进行验证,本研究对比摸索了3种触角的处理方法,并进行同一浓度（30 ng·μL^-1）二元混合物、不同配比的触角EAG测试。结果包括: 建立了一种鳃叶状触角的触角电位（EAG）测定方法,即将暗黑鳃金龟Holotrichia parallela触角的各鳃叶用针分离开后进行测定,这种方法测得的触角电位反应值较高。雄虫触角对L-异亮氨酸甲酯和(R)-(-)-芳樟醇为7∶1的二元混合物的反应值最高,和暗黑鳃金龟雌虫性信息素25个腺体提取液的EAG反应相当;对同一配比（7∶1）不同剂量刺激液的EAG测试表明,雄虫对浓度为30 ng·μL^-1的二元混合物刺激液的反应值最高。嗅觉反应结果进一步证实,试虫对L-异亮氨酸甲酯和(R)-(-)-芳樟醇7∶1的选择最高,选择系数达93.3%。研究结果为利用性信息素防治暗黑鳃金龟技术的开发提供了基础。     

靶向肿瘤新生血管纳米粒的构建和质量控制

目的：制备F56多肽修饰的长春新碱纳米粒（F56-VCR-NP）,并建立其质量控制方法。方法：乳化－溶剂挥发法优化制备F56．VCR-NP：HPLC法测定其载药量、包封率,透射电镜下观察其形态,激光粒度分析仪测定其粒径和Zeta电位,CBQCA试剂盒测定纳米粒表面多肽密度,XPS进行表面元素分析。结果：优化制备的F56－VCR-NP粒径约为153nm,Zeta电位为－20．8mv,包封率为21．4％,载药量为1．9％,多肽连接效率为26．3％。结论：以聚乙二醇－聚乳酸（PEG-PLA）为原料,长春新碱为模型药物,成功制备出纳米粒子,并建立起有效的质量控制方法,对该实验样品进行了表征。结果表明此类纳米粒子尺寸均匀,表面多价连接F56多肽,载药量和包封率稳定可控,工艺成熟。     

Antimicrobial activity of Curcuma xanthorrhiza nanoemulsions on Streptococcus mutans biofilms

Abstract

In this study, an optimal nanoemulsion formulation for Curcuma xanthorrhiza oil (Xan) was investigated using different sonication times. The antimicrobial effects of the nanoemulsion, the original emulsion, distilled water (DW), and Listerine, on Streptococcus mutans biofilms were compared. The optimum ultrasonic time, determined in terms of droplet size and stability, was found to be 10?min. Cell viability was the lowest on exposure to the nanoemulsion, and significantly different compared with exposure to DW or Listerine. The emulsion’s effect was similar to that of the nanoemulsion, but was non-uniform with a high interquartile range. Confocal microscope analysis revealed that the live/dead cell ratio in the nanoemulsion was 50% and 40% less than those in DW and Listerine, respectively. Biofilm treated with the nanoemulsion was thinner than biofilms exposed to the other treatments. Xan nanoemulsions exhibited stable and strong antimicrobial effects due to nano-sized particles, highlighting their potential use in oral health treatment.     

Stability of the oil-in-water type triacylglycerol emulsions

Lipid emulsions with saturated triacylglycerols (TAGs) with 4 to 10 carbons in each acyl chain were prepared to study how the oil component alters the stability of the lipid emulsions when phosphatidylcholines were used as emulsifiers. The average droplet size of the emulsions became smaller as the chain length of the TAG increased. For a given oil, emulsion with smaller droplets was formed with an emulsifier having higher HLB value. The influence of HLB values on the droplet size was biggest for the tributyrin (C4) emulsions. For the tricaprylin (C8) emulsions, droplet size was identical at given emulsifier concentrations regardless of HLB values. The HLB value and the concentration of the emulsifiers also affect the droplet size of the emulsions. The emulsions with smaller average droplet size were more stable than with bigger size for 20 days. The oil and water (o/w) interfacial tension is inversely proportional to the initial droplet size of the emulsion.     

Nanoemulsions as vehicles for transdermal delivery of aceclofenac

The aim of the present study was to investigate the potential of a nanoemulsion formulation for transdermal delivery of aceclofenac. Various oil-in-water nanoemulsions were prepared by the spontaneous emulsification method. The nanoemulsion area was identified by constructing pseudoternary phase diagrams. The prepared nanoemulsions were subjected to different thermodynamic stability tests. The nanoemulsion formulations that passed thermodynamic stability tests were characterized for viscosity, droplet size, transmission electron microscopy, and refractive index. Transdermal permeation of aceclofenac through rat abdominal skin was determined by Franz diffusion cell. The in vitro skin permeation profile of optimized formulations was compared with that of aceclofenac conventional gel and nanoemulsion gel. A significant increase in permeability parameters such as steady-state flux (J(ss)), permeability coefficient (K(p)), and enhancement ratio (E(r)) was observed in optimized nanoemulsion formulation F1, which consisted of 2% wt/wt of aceclofenac, 10% wt/wt of Labrafil, 5% wt/wt of Triacetin, 35.33% wt/wt of Tween 80, 17.66% wt/wt of Transcutol P, and 32% wt/wt of distilled water. The anti-inflammatory effects of formulation F1 showed a significant increase (P < .05) in percent inhibition value after 24 hours when compared with aceclofenac conventional gel and nanoemulsion gel on carrageenan-induced paw edema in rats. These results suggested that nanoemulsions are potential vehicles for improved transdermal delivery of aceclofenac.     

Development,Optimization, and Characterization of PEGylated Nanoemulsion of Prostaglandin E1 for Long Circulation

Lipo-PGE1 is the most widely used formulation of PGE1 in clinic. However, PGE1 is easier to leak out from lipo-PGE1 and this will lead to the phlebophlogosis when intravenous injection. The stability of lipo-PGE1 in storage and in vivo is also discounted. The aim of this study is to develop a long-circulating prostaglandin E1-loaded nanoemulsion modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) to improve the stability and pharmacokinetics profiles of lipo-PGE1. PEGylated PGE1 nanoemulsion was prepared using a dispersing-homogenized method. The stability of nanoemulsion in 1 month was investigated. Pharmacokinetic studies were employed to evaluate the in vivo profile of the optimized nanoemulsion. The optimized nanoemulsion PGE1-PEG2000(1%)-NE showed an oil droplet size <100 nm with a surface charge of ?14 mV. Approximately, 97% of the PGE1 was encapsulated in the nanoemulsion. The particle size, zeta potential, and drug loading of PGE1-PEG2000(1%)-NE were stable in 1 month. After PGE1-PEG2000(1%)-NE was intravenously administered to rats, the area under curve (AUC) and half-life of PGE1 were, respectively, 1.47-fold and 5.98-fold higher than those of lipo-PGE1 (commercial formulation). PGE1-PEG2000(1%)-NE was an ideal formulation for prolonging the elimination time of PGE1. This novel parenteral colloidal delivery system of PGE1 has a promising potential in clinic use.     

Evaluation of the Stability of Concentrated Emulsions for Lemon Beverages Using Sequential Experimental Designs

The study of the stability of concentrated oil-in-water emulsions is imperative to provide a scientific approach for an important problem in the beverage industry, contributing to abolish the empiricism still present nowadays. The use of these emulsions would directly imply a reduction of transportation costs between production and the sales points, where dilution takes place. The goal of this research was to evaluate the influence of the main components of a lemon emulsion on its stability, aiming to maximize the concentration of oil in the beverage and to correlate its physicochemical characteristics to product stability, allowing an increase of shelf life of the final product. For this purpose, analyses of surface and interface tension, electrokinetic potential, particle size and rheological properties of the emulsions were conducted. A 2^4-1 fractional factorial design was performed with the following variables: lemon oil/water ratio (30% to 50%), starch and Arabic gum concentrations (0% to 30%) and dioctyl sodium sulfosuccinate (0 mg/L to 100 mg/L), including an evaluation of the responses at the central conditions of each variable. Sequentially, a full design was prepared to evaluate the two most influential variables obtained in the first plan, in which concentration of starch and gum ranged from 0% to 20%, while concentration of lemon oil/water ratio was fixed at 50%, without dioctyl sodium sulfosuccinate. Concentrated emulsions with stability superior to 15 days were obtained with either starch or Arabic gum and 50% lemon oil. The most stable formulations presented viscosity over 100 cP and ratio between the surface tension of the emulsion and the mucilage of over 1. These two answers were selected, since they better represent the behavior of emulsions in terms of stability and could be used as tools for an initial selection of the most promising formulations.     

Use of artificial neural networks for analysis of the factors affecting particle size in mebudipine nanoemulsion

In this study, a nanoemulsion containing mebudipine [composed of ethyl oleate (oil phase), Tween 80 (T80), Span 80 (S80) (surfactants), polyethylene glycol 400, ethanol (cosurfactants), and deionized water] was prepared with the aim of improving its bioavailability for an effective antihypertensive therapy. Particle size of the formulation was measured by dynamic light scattering. Then, artificial neural networks were used in identifying factors that influence the particle size of the nanoemulsion. Three variables, namely, amount of surfactant system (T80?+?S80), amount of polyethylene glycol, and amount of ethanol as cosurfactants, were considered as input values and the particle size was used as output. The developed model showed that all the three inputs had some degrees of effect on particles size: increasing the value of each input decreased the size. Furthermore, amount of surfactant was found to be the dominant factor in controlling the final particle size of nanoemulsion.

Communicated by Ramaswamy H. Sarma     

Development and Evaluation of Emulsions from <Emphasis Type="Italic">Carapa guianensis</Emphasis> (Andiroba) Oil

Carapa guianensis, a popular medicinal plant known as “Andiroba” in Brazil, has been used in traditional medicine as an insect repellent and anti-inflammatory product. Additionally, this seed oil has been reported in the literature as a repellent against Aedes aegypti. The aim of this work is to report on the emulsification of vegetable oils such as “Andiroba” oil by using a blend of nonionic surfactants (Span 80® and Tween 20®), using the critical hydrophilic–lipophilic balance (HLB) and pseudo-ternary diagram as tools to evaluate the system’s stability. The emulsions were prepared by the inverse phase method. Several formulations were made according to a HLB spreadsheet design (from 4.3 to 16.7), and the products were stored at 25°C and 4°C. The emulsion stabilities were tested both long- and short-term, and the more stable one was used for the pseudo-ternary diagram study. The emulsions were successfully obtained by a couple of surfactants, and the HLB analysis showed that the required HLB of the oil was 16.7. To conclude, the pseudo-ternary diagram identified several characteristic regions such as emulsion, micro-emulsion, and separation of phases.     

Oxidative kinetics of salmon oil in bulk and in nanoemulsion stabilized by marine lecithin

Salmon oil (Salmo salar) rich in long-chain polyunsaturated fatty acids was submitted to various oxidative stresses (temperature, atmosphere, presence of natural antioxidant or pro-oxidant). Oxidative kinetics of oil formulations and nanoemulsions prepared by high-pressure homogenization (1700 bars) were carried out by using conjugated dienes and infrared spectroscopy measurements. Droplet size nanoemulsion and polyene index were calculated from the fatty acid composition of oils, and the lipid fraction of emulsions were followed up over a period of 40 days.The particle size of different nanoemulsions was about 160–207 nm. The oxidative stability of salmon lecithin was higher than that of other oil samples in spite of its high LC-PUFA concentration. Crude salmon oil was better protected by its natural antioxidants (tocopherols and astaxanthin). In this study, a high concentration of α-tocopherol (0.2%) was used for its pro-oxidant role. The addition of quercetin improves slightly the oxidative stability of oils. However, no effect of this antioxidant was observed in emulsion, due to its insolubility in water and lipid phases.     

Development and characterization of a carvacrol nanoemulsion and evaluation of its antimicrobial activity against selected food-related pathogens

Carvacrol has been recognized as an efficient growth inhibitor of food pathogens. However, carvacrol oil is poorly water-soluble and can be oxidized, decomposed or evaporated when exposed to the air, light, or heat. To overcome these limitations, a carvacrol nanoemulsion was developed and its antimicrobial activity against food pathogens evaluated in this study. The nanoemulsion containing 3% carvacrol oil, 9% surfactants (HLB 11) and 88% water, presented good stability over a period of 90 days. In general, the carvacrol nanoemulsion (MIC: 256 µg ml⁻¹ for E. coli and Salmonella spp., 128 µg ml⁻¹ for Staphylococcus aureus and Pseudomonas aeruginosa) exhibited improved antimicrobial activity compared to the free oil. The carvacrol nanoemulsion additionally displayed bactericidal activity against Escherichia coli, P. aeruginosa and Salmonella spp. Therefore, the results of this study indicated that carvacrol oil nanoemulsions can potentially be incorporated into food formulations, wherein their efficacy for the prevention and control of microbial growth could be evaluated.     

Investigating the Parameters Affecting the Stability of Superparamagnetic Iron Oxide-Loaded Nanoemulsion Using Artificial Neural Networks

Nanoemulsions are increasingly being investigated for their fascinating capability of loading both hydrophobic and hydrophilic molecules while their stability is still an issue, being affected by various factors. In this study, to evaluate the dominant factors affecting the stability of nanoemulsions, artificial neural networks (ANNs) were implemented. Nanoemulsions of almond oil in water containing oleic acid-coated superparamagnetic iron oxide nanoparticles were prepared using a mixture of Tween 80 and Span 80 as surfactant system and ethanol as a co-surfactant. The ratio of transparency of the samples at 30 min and 7 days after preparation was taken as an indication of the stability of samples. Four independent variables, namely, concentration of nanoparticle, surfactant, oil, and alcohol were investigated to find their relations with the dependent variable (i.e., transparency ratio). Using ANNs modeling, it was concluded that the stability is affected by all variables, with all variables showing reverse effect on the stability beyond an optimum amount.Key words: artificial neural networks, nanoemulsion, optimization, stability, superparamagnetic iron oxide