二十八烷醇微乳液的毒理学评价

二十八烷醇微乳液是由二十八烷醇、吐温80、乙醇等配制而成的均一透明液体。通过急性毒性经口试验和28 d经口重复毒性试验,判断二十八烷醇微乳液的食品毒性。在急性毒理学试验中,对昆明小鼠一次性经口灌胃10 g/kg bw二十八烷醇微乳液,观察14 d,无中毒或死亡症状,LD50>10 g/kg bw,属于实际无毒级别。在28 d经口重复毒性试验中,设置二十八烷醇高剂量组(5.00 g/kg bw)、中剂量组(2.50 g/kg bw)、低剂量组(1.25 g/kg bw)和阴性对照组,通过临床观察、对比体质量和摄食量变化、进行血液学、血生化及病理学检查得出结论,二十八烷醇微乳液对小鼠最大无作用剂量为2.50 g/kg bw(人体推荐摄入量的100倍)。综上所述,二十八烷醇微乳液无毒。     

The bioavailability of an omega‐3‐rich algal oil is improved by nanoemulsion technology using yogurt as a food vehicle

Global trends show that habitual omega‐3 intakes are short of recommended guidelines, particularly among vegetarians. Subsequently, alternative dietary sources of long‐chain omega‐3 polyunsaturated fatty acids (LC3PUFA) from vegetarian sources are needed. Food technology methods are advancing, and nanoemulsion technologies have improved the bioavailability of certain lipid‐based nutrients. This study examined whether ingestion of an omega‐3 algal oil nanoemulsion led to improved bioavailability compared to the bulk oil. Eleven subjects completed a single‐blind, randomised crossover trial, with a 21‐day washout between interventions. Results demonstrated that LC3PUFA absorption from the nanoemulsion was significantly higher than the bulk oil. Percentage blood fatty acids were significantly increased for docosahexaenoic acid (DHA; P ≤ 0.05) while LC3PUFA: PUFA ratios increased (P ≤ 0.05) and omega‐6:omega‐3 ratios were reduced (P = 0.028). Larger and longer intervention studies are now needed, but these preliminary findings demonstrate that nanoemulsion technology may improve the absorption of omega‐3 fatty acids.     

Enhanced stability and permeation potential of nanoemulsion containing sefsol-218 oil for topical delivery of amphotericin B

Aim: To characterize the enhanced stability and permeation potential of amphotericin B nanoemulsion comprising sefsol-218 oil at varying pH and temperature of aqueous continuous phase.

Methodology: Several batches of amphotericin B loaded nanoemulsion were prepared and evaluated for their physical and chemical stability at different pH and temperature. Also, a comparative study of ex vivo drug permeation across the albino rat skin was investigated with commercial Fungisome® and drug solution at 37?°C for 24?h. The extent of drug penetrated through the rat skin was thereby evaluated using the confocal laser scanning microscopy (CLSM).

Results and conclusions: The optimized nanoemulsion demonstrated the highest flux rate 17.85?±?0.5?µg/cm²/h than drug solution (5.37?±?0.01?µg/cm²/h) and Fungisome® (7.97?±?0.01?µg/cm²/h). Ex vivo drug penetration mechanism from the developed formulations at pH 6.8 and pH 7.4 of aqueous phase pH using the CLSM revealed enhanced penetration. Ex vivo drug penetration studies of developed formulation comprising of CLSM revealed enhanced penetration in aqueous phase at pH 6.8 and 7.4. The aggregation behavior of nanoemulsion at both the pH was found to be minimum and non-nephrotoxic. The stability of amphotericin B was obtained in terms of pH, optical density, globular size, polydispersity index and zeta potential value at different temperature for 90 days. The slowest drug degradation was observed in aqueous phase at pH 7.4 with shelf life 20.03-folds higher when stored at 4?°C (3.8 years) and 5-fold higher at 25?°C (0.951 years) than at 40?°C. The combined results suggested that nanoemulsion may hold an alternative for enhanced and sustained topical delivery system for amphotericin B.     

蛇油纳米乳的制备及稳定性评价

通过水相滴定法制备蛇油纳米乳,研究了混合油相、表面活性剂、助表面活性剂对蛇油纳米乳制备的影响,并利用伪三元相图法确定最佳蛇油纳米乳配方。结果表明：混合油相选择蛇油和肉豆蔻酸异丙酯（IPM）,表面活性剂选择Span80和Tween80二者质量比27∶ 73,助表面活性剂选择PEG400;最佳蛇油纳米乳配方为蛇油1.6 g、IPM 2.4 g、Span80 1.08 g、Tween80 2.92 g、PEG400 4.0 g、水8.0 g。所制得的蛇油纳米乳为O/W型,平均粒径为63.01 nm,PDI为0.226,Zeta电位为-19 mV,液滴外观为圆形,粒径均匀且状态良好;离心后清澈透明,不分层;不耐高温,需要在25 ℃以下贮存;冷冻后,可以在室温下恢复到初始状态;氧化稳定性较蛇油提高     

复方联苯苄唑纳米乳的制备及其质量评价

以联苯苄唑为主药,辅以丙酸氯倍他索以及肉桂醛制成复方。通过绘制伪三元相图筛选处方研制复方联苯苄唑纳米乳,并对其进行质量评价。结果表明,复方联苯苄唑纳米乳最佳配方为:w(联苯苄唑)=1.6%,w(丙酸氯倍他索)=0.05%,w(肉桂醛)=0.15%,w(吐温-80)=29.5%,w(无水乙醇)=9.8%,w(乙酸乙酯)=13.6%,w(蒸馏水)=45.3%。该纳米乳为水包油型纳米乳,可用水无限稀释。透射电镜下,纳米乳呈圆球形,无粘连。平均粒径(Z-Average)为10.4 nm,多分散系数(PDI)为0.196。在25℃时,稀释5倍后的复方联苯苄唑纳米乳的平均pH=6.1±0.3,对应的平均Zeta电位为(-9.18±0.2)mV。复方联苯苄唑纳米乳制备工艺简单且质量可控,有望应用于临床。     

纳米乳液提高氧化白藜芦醇口服生物利用率及透皮吸收效率

本研究制备纳米乳液改善氧化白藜芦醇在水溶液中的溶解性能,通过体外药物溶出实验、脂解实验、Caco-2跨膜细胞转运实验、透皮吸收实验评价了纳米乳液对氧化白藜芦醇生物利用率的改善效果。结果表明:氧化白藜芦醇纳米乳液和氧化白藜芦醇化合物自身的生物利用率在进食状态下分别为61.22%和23.47%,禁食状态下为56.12%和22.45%。纳米乳液使氧化白藜芦醇在小肠上皮细胞的扩散速度由中速上升至快速,扩散形式为被动渗透,表观渗透系数Papp(AP-BL)值1.69×10^-5 cm/sec,Papp(BL-AP)值8.94×10^-6cm/sec,ER=Rpapp(AP-BL)/(BL-AP)=1.89。6 h时氧化白藜芦醇纳米乳液和化合物的经皮扩散透过量分别为51.76和5.73μg/cm^2 skin。结论:氧化白藜芦醇纳米乳液比化合物本身的生物利用率提升了3倍,显著提升氧化白藜芦醇在小肠上皮细胞内的吸收转运量(提升2~4倍)和透皮吸收效率(p<0.05),本实验为氧化白藜芦醇的应用奠定研究基础,为其有效地发挥生物活性提供理论依据。     

高压微射流制备岩藻黄素纳米乳液的影响因素及其理化分析

采用高压微射流制备岩藻黄素纳米乳液（fucoxanthin nanoemulsion,FCNE）,研究均质条件、乳化剂类型和质量分数、乳化温度、助乳化剂（甘油）对FCNE理化性质的影响。结果表明：FCNE粒径和多分散指数（polydispersity index,PDI）随均质压强和次数的增加而减小,压强120 MPa、均质4 次后FCNE粒径基本达到最小（154 nm,PDI=0.19）。不同乳化剂（吐温80、十二烷基硫酸钠（sodium dodecyl sulfate,SDS）、酪蛋白酸钠）制备的FCNE粒径大小为：SDS＜吐温80＜酪蛋白酸钠,且随着乳化剂质量分数和乳化温度的升高,FCNE粒径显著减小（P＜0.05）。此外,添加不同质量分数的甘油后,吐温80和SDS制备的FCNE粒径显著减小（P＜0.05）,而酪蛋白酸钠制备的FCNE粒径变化较小,表明SDS和吐温80制备的FCNE比酪蛋白酸钠制备的FCNE对水相黏度变化更敏感。在不同的pH值条件下,吐温80制备的FCNE可稳定存在,表面电荷基本不变;而SDS和酪蛋白酸钠制备的FCNE在酸性条件下稳定性较差,且pH值从7变化至3时,其粒径变化显著（P＜0.05）。在37 ℃条件下储存30 d后,纳米乳液中岩藻黄素残留量明显高于有机相,表明将岩藻黄素制成FCNE显著提高了岩藻黄素的储存稳定性。     

Ovarian Accumulation of Nanoemulsions: Impact of Mice Age and Particle Size

Nanotechnology in the field of drug delivery comes with great benefits due to the unique physicochemical properties of newly developed nanocarriers. However, they may come as well with severe toxicological side effects because of unwanted accumulation in organs outside of their targeted site of actions. Several studies showed an unintended accumulation of various nanocarriers in female sex organs, especially in the ovaries. Some led to inflammation, fibrosis, or decreasing follicle numbers. However, none of these studies investigated ovarian accumulation in context to both reproductive aging and particle size. Besides the influences of particle size, the biodistribution profile may be altered as well by reproductive aging because of reduced capacities of the reticuloendothelial system (RES), changes in sex steroid hormone levels as well as altering ovarian stromal blood flow. This systematic investigation of the biodistribution of intravenously (i.v) injected nanoemulsions revealed significant dependencies on the two parameters particle size and age starting from juvenile prepubescent to senescent mice. Using fluorescent in vivo and ex vivo imaging, prepubescent mice showed nearly no accumulation of nanoemulsion in their uteri and ovaries, but high accumulations in the organs of the RES liver and spleen independently of the particle size. In fertile adult mice, the accumulation increased significantly in the ovaries with an increased particle size of the nanoemulsions by nearly doubling the portion of the average radiant efficiency (PARE) to ~10% of the total measured signal of all excised organs. With reproductive aging and hence loss of fertility in senescent mice, the accumulation decreased again to moderate levels, again independently of the particle size. In conclusion, the ovarian accumulation of these nanocarriers depended on both the age plus the particle size during maturity.     

薄荷油纳米乳液的制备及其性质分析

为克服薄荷油易挥发、不易溶于水的缺点,以大豆分离蛋白-磷脂酰胆碱复合物作为乳化剂,采用高压均质法制备薄荷油纳米乳液,研究大豆分离蛋白质量分数、薄荷油质量分数及均质压力对薄荷油纳米乳液的平均粒径、多分散性指数、Zeta电位、浊度、乳化产率、乳液稳定性指数的影响,并确定制备薄荷油纳米乳液的最佳工艺参数为：大豆分离蛋白质量分数2.5%、薄荷油质量分数5%、均质压力80 MPa。通过动态光散射和透射电镜验证最佳条件制备的薄荷油纳米乳液平均粒径小且分布均匀;通过气相色谱-质谱检测发现大豆蛋白-磷脂酰胆碱为乳化剂制备的纳米乳液可有效保护薄荷油功能成分;流变学特性结果表明薄荷油纳米乳液具有良好的动力学稳定性。