Development of a nanoemulsion of Phyllanthus emblica L. branch extract

For potential topical administration, we formulated a nanoemulsion containing phenolic constituents of Phyllanthus emblica branch extract. The nanoemulsion has high entrapment efficiency, small particle size, is stable, and can release its main chemical components. Branches of P. emblica were extracted with 50% ethanol (EPE) with 5.4% yield. HPLC analysis indicated several phenolic compounds, including gallic acid, vanillic acid, epigallocatechin (EGC), epigallocatechin gallate (EGCG) and ellagic acid. These were selected as chemical markers of EPE in the nanoemulsion development. The nanoemulsion was prepared by microemulsion techniques with hot high pressure homogenization. A ternary phase diagram was constructed to obtain the optimized nanoemulsion. The obtained transparent EPE nanoemulsion is composed of isopropyl myristate (0.6% w/w), Brij® 78 (0.35% w/w), and 0.15% (w/w) EPE. The optimized EPE nanoemulsion had a median particle size of 191.63?±?4.07?nm with a narrow particle size distribution, a zeta potential of ?10.19?±?0.54?mV, high entrapment efficiency at 67.99?±?0.87% and good stability at 4?°C after 90?d of storage. The release of active ingredients from the EPE nanoemulsion was slower than that of the EPE aqueous formulation. The loading ratios of the five phenolic compounds were high, with relative order of EGC?>?EGCG?>?vanillic acid?>?gallic acid?>?ellagic acid, resulting in slow release profiles of EGC and EGCG in the EPE nanoemulsion. In conclusion, the obtained EPE nanoemulsion has good characteristics for future clinical trials.     

Design and development of a novel pH triggered nanoemulsified in-situ ophthalmic gel of fluconazole: Ex-vivo transcorneal permeation,corneal toxicity and irritation testing

The objective of the present research was to develop a novel pH triggered nanoemulsified in-situ gel (NE-ISG) for ophthalmic delivery of fluconazole (FLZ) to enhance the permeation and residence time of the formulation, by overcoming the limitations associated with protective ocular barriers. Pseudoternary phase diagrams were constructed using capmul MCM (oil phase), tween 80 (surfactant) and transcutol P (cosurfactant) to identify the NE region. Nanoemulsions (NE1-NE6) of FLZ were prepared by spontaneous emulsification method and evaluated for various pharmacotechnical characteristics. NE4 was selected as optimized NE and was dispersed in carbopol 934 solution to form nanoemulsified sols (NE-ISG1 to NE-ISG5) that were expected to convert in to in-situ gels at corneal pH (7.4). The optimized NE-ISG was selected on the basis of gelation ability with a residence time up to or more than 6?h. Ex-vivo transcorneal permeation study displayed significantly higher (p?<?0.05) permeation of FLZ from NE-ISG5 (337.67 µg/cm²) and NE4 (419.30 µg/cm²) than the commercial eye drops (112.92 µg/cm²). Hen’s egg test-Chorioallantoic membrane (HET-CAM) test with zero score indicated the non-irritant property of developed NE-ISG5. Corneal toxicity study revealed no visual signs of tissue damage. Hence it can be concluded that NE-ISG5 may offer a more intensive treatment of ocular fungal infections due to higher permeation, prolonged precorneal residence time and sustained drug release along with higher in-vitro efficacy, safety and greater patient compliance.     

Development of dorzolamide hydrochloride in situ gel nanoemulsion for ocular delivery

Background: Several in situ gel-forming systems have been developed to prolong the precorneal residence time of a drug and to improve ocular bioavailability. Poloxamer 407 with its thermoreversible gelation and surface active properties was utilized to formulate a novel dorzolamide hydrochloride in situ gel nanoemulsion (NE) delivery system for ocular use. Objective: Improvement of both ocular bioavailability and duration of action for dorzolamide hydrochloride was the aim of this study. Methods: Physicochemical properties, in vitro drug release studies and biological evaluation of the prepared NEs were investigated. Results: The optimum formulation of in situ gel NE consisted of Triacetin (7.80%), Poloxamer 407 (13.65%), Poloxamer 188 (3.41%), Miranol C2M (4.55%), and water (70.59%). Biological evaluation of the designed dorzolamide formulation on normotensive albino rabbits indicated that this formulation had better biological performance, faster onset of action, and prolonged effect relative to either drug solution or the market product. The formula showed a superior pharmacodynamic activity compared to the in situ gel dorzolamide eye drops. This indicated the effectiveness of the in situ gel properties of poloxamer 407, besides formulating the drug in an NE form for improving the therapeutic efficacy of the drug. Conclusion: These results demonstrate the superiority of in situ gel NE to conventional ocular eye drops and in situ gels to enhance ocular drug bioavailability.     

Nanoemulsions: Synthesis,Characterization, and Application in Bio‐Based Active Food Packaging

The increasing demands for foods with fresh‐like characteristics, lower synthetic additive and preservative contents, and low environmental footprint, but still safe to consume, have guided researchers and industries toward the development of milder processing technologies and more eco‐friendly packaging solutions. As sustainability acquires an increasingly critical relevance in food packaging, bio‐based and/or biodegradable materials stand out as suitable alternatives to their synthetic counterparts. In this context, the use of nanoemulsions has represented a step forward for improving the performance of sustainable food packaging devices, especially for the successful incorporation of new compounds and functionalities into conventional films and coatings. This class of emulsions, featuring unique optical stability and rheological properties, has been developed to protect, encapsulate, and deliver hydrophobic bioactive and functional compounds, including natural preservatives (such as essential oils from plants), nutraceuticals, vitamins, colors, and flavors. This article presents the surfactants (including naturally occurring proteins and carbohydrates), dispersants, and oil‐soluble functional compounds used for designing food‐grade nanoemulsions intended for packaging applications. The improved kinetic stability, bioavailability, and optical transparency of nanoemulsions over conventional emulsions are discussed considering theoretical concepts and real experiments. Bottom‐up and top‐down approaches of nanoemulsion fabrication are described, including high‐energy (such as high‐pressure homogenizers, microfluidics, ultrasound, and high‐speed devices) and low‐energy methods (for instance, phase inversion and spontaneous emulsification). Finally, incorporation of nanoemulsions in biopolymer matrixes intended for food packaging applications is also addressed, considering current characterization techniques as well as their potential antimicrobial activity against foodborne pathogens.     

响应面法优化超声乳化制备油茶籽油纳米乳液及其稳定性研究

以Tween80为乳化剂,研究了超声功率、油茶籽油体积分数、乳油比及其交互作用对超声乳化制备油茶籽油纳米乳液平均粒径及多分散指数的影响,利用响应面法优化了制备条件并对油茶籽油纳米乳液的稳定性进行初步评价。结果表明:油茶籽油纳米乳液的平均粒径及多分散指数模型拟合度R~2分别为0.974 2和0.951 9;最优制备条件为超声功率405 W、超声时间15 min、油茶籽油体积分数8.3%、乳油比0.16∶1,在该条件下油茶籽油纳米乳液的平均粒径为(74.9±0.85)nm,多分散指数为0.17±0.01;贮存温度、贮存时间及二者的交互作用对油茶籽油纳米乳液的平均粒径及多分散指数有极显著影响(P0.01),油茶籽油纳米乳液在5℃和25℃条件下贮存60 d,其平均粒径小于90 nm,多分散指数小于0.3,表现出了较好的动力学稳定性。     

不同大分子乳化剂构建番茄红素纳米乳液的体外消化规律比较

通过体外模拟消化,研究以辛烯基琥珀酸酯化（octenyl succinic anhydride,OSA）变性淀粉、乳清分离蛋白（whey protein isolate,WPI）、酪蛋白酸钠（sodium caseinate,SC）为乳化剂构建的番茄红素纳米乳液的消化规律。结果表明,消化过程中纳米乳液的液滴大小、Zeta电位和微观结构取决于乳化剂类型,OSA变性淀粉和蛋白质类乳化剂构建的纳米乳液分别在肠和胃阶段发生水解,液滴聚集,乳液平均粒径增大,同时Zeta电位绝对值达到最小。经胃肠消化后3 种乳化剂构建的番茄红素纳米乳液游离脂肪酸释放率的大小排序为OSA变性淀粉（92.25%）＞SC（86.53%）＞WPI（79.88%）,高于对照组的48.7%,表明纳米乳液包埋体系能有效改善番茄红素的消化特性,且以OSA变性淀粉构建的纳米乳液表现出比蛋白质类乳化剂更高的番茄红素生物利用率,达到（25.60±3.08）%。     

环境因素对叶黄素纳米乳液稳定性及其抗氧化活性的影响

以酪蛋白酸钠为乳化剂,高压均质构建叶黄素纳米乳液载运体系,并评价其对1,1-二苯基-2-三硝基苯肼自由基和2,2’-联氮-二(3-乙基-苯并噻唑-6-磺酸)阳离子自由基的清除能力和氧自由基吸收能力,及环境因素（pH值、热处理、离子强度和浓缩）对乳液体系中叶黄素稳定性和自由基清除活性的影响。结果表明：纳米乳液体系能够显著提高叶黄素的自由基清除活性（P＜0.05）;pH值为2.0或离子强度为50 mmol/L和100 mmol/L NaCl时,纳米乳液的叶黄素质量浓度和自由基清除活性有不同程度的减小,旋转蒸发浓缩后叶黄素质量浓度和自由基清除率均显著增加（P＜0.05）,而热处理（60、80 ℃和100 ℃）对叶黄素纳米乳液体系的影响则相对较小。     

Design and optimization of thermosensitive nanoemulsion hydrogel for sustained-release of praziquantel

Objective: This work aimed to develop an alternative sustained-release thermosensitive praziquantel-loaded nanoemulsion (PZQ-NE) hydrogel for better schistosomiasis treatment.

Significance: PZQ-NE-dispersed chitosan/glycerol 2-phosphate disodium/HPMC (NE/CS/β-GP/HMPC) hydrogel was successfully prepared to improve bioavailability of PZQ.

Methods: Solubility tests and pseudo-ternary phase diagrams were applied to screen optimal oils, surfactants and co-surfactants of NE. The hydrogels were characterized for gelling time, surface exudates, rheological properties and in vitro drug release. Formulation optimization of NE/CS/β-GP/HMPC hydrogel was conducted by Box–Behnken experimental design combined with response surface methodology. In vitro cytotoxicity of hydrogel was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. The sustained-release property of PZQ in NE and optimized hydrogel was evaluated by pharmacokinetic study in rabbits.

Results: The formulation of PZQ-NE consisted of mass ratio of 12.5% capryol 90 containing PZQ (160?mg/g), 40% cremophor RH 40/tween 20 and transcutol HP (S/CoS?=?2:1), 47.5% deionized water. PZQ releasing from NE/CS/β-GP/HMPC hydrogels was best fitted to Higuchi model and governed by diffusion. Rheological investigation evidenced the themosensitive gelation of different hydrogel systems and their gel-like character at 37?°C. The optimized hydrogel formulation consisted of HPMC solution (103.69?mg/g), 3.03% (w/v) chitosan and 14.1% (w/v) β-GP showed no cytotoxicity when the addition of NE was no more than 100?mg/g. Pharmacokinetic parameters indicated that NE/CS/β-GP/HMPC hydrogel can significantly slow down drug elimination, prolong mean residence time and improve bioavailability of PZQ.

Conclusions: NE/CS/β-GP/HMPC hydrogel possessed sustained-release property and could be an alternative antischistosomal drug delivery system with improved therapeutic effect.     

Experimental investigation of water-in-oil nanoemulsion in sinking electrical discharge machining

The most common dielectric in sinking electrical discharge machining (EDM) is kerosene. However, kerosene is inflammable; besides, it can be decomposed and release harmful gases during machining process. And, owing to its low viscosity, using kerosene in sinking EDM has low machining efficiency. Accordingly, conventional sinking EDM using kerosene as dielectric has poor safety, unfriendly environment impact, and low machining efficiency. A new water-in-oil (W/O) nanoemulsion is presented in this paper. This W/O nanoemulsion not only can eliminate the hazards from kerosene to operator and environment but also improve the machining performance of conventional sinking EDM. This research aims to experimentally investigate the machining performance of W/O nanoemulsion in comparison with kerosene in sinking EDM at relatively low discharge energy. The effects of electrode material, electrode polarity, peak current, and pulse duration on machining performance are studied. The machined surface and recast layer of workpiece are characterized as well. The experimental results demonstrate that compared with kerosene, using W/O nanoemulsion in sinking EDM can obtain a higher material removal rate (MRR), a lower relative electrode wear rate (REWR), and a machined workpiece with fewer defects and thinner recast layer.     

肉桂精油纳米乳液制备工艺研究

研究了肉桂精油和中链脂肪甘油为油相、变性淀粉辛烯基琥珀酸淀粉酯等乳化剂制备纳米乳液的工艺条件。采用正交试验设计方法,以乳液颗粒直径大小为指标优选高压均质法参数条件,Turbiscan浓缩体系稳定性分析仪分析纳米乳液粒径大小及稳定性变化趋势。结果表明,乳化剂质量百分比20%,油相质量百分比10%,肉桂精油和中链脂肪甘油质量比1:3,均质压力为100 MPa,循环均质6次的工艺条件下可得到粒径大小为90~120 nm的水包油相纳米乳化液且颗粒大小一致,储藏过程中不出现上浮和沉淀等不稳定现象。气相色谱-质谱分析鉴定了出肉桂精油总含量的99.64%,再应用峰面积归一法计算各组分的相对百分含量,得出精油中主要的成分化合物有肉桂醛、肉桂酸、α-蒎烯、邻甲氧基肉桂醛、α-依兰烯和α-毕橙茄醇等未发生明显变化。通过添加83%(m/m)中链脂肪甘油在油相中有助于延缓乳化液中奥氏熟化现象,在低温条件放置15 d肉桂精油保留率保持在85%以上。