大豆分离蛋白-甜菊糖苷复合稳定剂制备纳米乳液

为适应食品工业对食品配料天然绿色、营养健康的追求,采用大豆分离蛋白（soy protein isolate,SPI）-甜菊糖苷（steviol glycosides,STE）复合体系作为稳定剂制备纳米乳液,研究稳定剂组成、微射流参数、油相质量分数等对纳米乳液形成的影响,并对乳液稳定性及微结构进行表征。结果表明：油相质量分数为10%时,单独SPI（1%）制备的乳液粒度较大（d43为0.548 μm）,稳定性差。添加0.25%～1% STE时,乳液粒度分布更均匀,粒度变小;当STE质量分数为0.5%和1%时,乳液粒度小于200 nm,且具备较好的贮存稳定性（30 d）。添加2% STE会导致乳滴表面蛋白被完全取代,从而弱化乳液的长期稳定性。微射流压力、均质次数及STE质量分数的增加均可降低乳液粒度,但油相质量分数的增加可增加乳液粒度。进一步将纳米乳液进行冷冻干燥处理,可制得结构化良好且高油含量的油粉;相对于单独SPI稳定的结构化乳液,SPI-STE纳米乳液制得的油粉结构更为完整,表面黏性小。     

A Versatile Theranostic Nanoemulsion for Architecture‐Dependent Multimodal Imaging and Dually Augmented Photodynamic Therapy

To design a clinically translatable nanomedicine for photodynamic theranostics, the ingredients should be carefully considered. A high content of nanocarriers may cause extra toxicity in metabolism, and multiple theranostic agents would complicate the preparation process. These issues would be of less concern if the nanocarrier itself has most of the theranostic functions. In this work, a poly(ethylene glycol)‐boron dipyrromethene amphiphile (PEG‐F₅₄‐BODIPY) with 54 fluorine‐19 (¹⁹F) is synthesized and employed to emulsify perfluorohexane (PFH) into a theranostic nanoemulsion (PFH@PEG‐F₅₄‐BODIPY). The as‐prepared PFH@PEG‐F₅₄‐BODIPY can perform architecture‐dependent fluorescence/photoacoustic/¹⁹F magnetic resonance multimodal imaging, providing more information about the in vivo structure evolution of nanomedicine. Importantly, this nanoemulsion significantly enhances the therapeutic effect of BODIPY through both the high oxygen dissolving capability and less self‐quenching of BODIPY molecules. More interestingly, PFH@PEG‐F₅₄‐BODIPY shows high level of tumor accumulation and long tumor retention time, allowing a repeated light irradiation after a single‐dose intravenous injection. The “all‐in‐one” photodynamic theranostic nanoemulsion has simple composition, remarkable theranostic efficacy, and novel treatment pattern, and thus presents an intriguing avenue to developing clinically translatable theranostic agents.     

Curcumin nanoemulsion for transdermal application: formulation and evaluation

The aim of this work is to develop a curcumin nanoemulsion for transdermal delivery. The incorporation of curcumin inside a nanoglobul should improve curcumin stability and permeability. A nanoemulsion was prepared by the self-nanoemulsification method, using an oil phase of glyceryl monooleate, Cremophor RH40 and polyethylene glycol 400. Evaluation of the nanoemulsion included analysis of particle size, polydispersity index, zeta potential, physical stability, Raman spectrum and morphology. In addition, the physical performance of the nanoemulsion in Viscolam AT 100P gel was studied. A modified vertical diffusion cell and shed snake skin of Python reticulatus were used to study the in vitro permeation of curcumin. A spontaneously formed stable nanoemulsion has a loading capacity of 350?mg curcumin/10?g of oil phase. The mean droplet diameter, polydispersity index and zeta potential of optimized nanoemulsion were 85.0?±?1.5?nm, 0.18?±?0.0 and ?5.9?±?0.3?mV, respectively. Curcumin in a nanoemulsion was more stable than unencapsulated curcumin. Furthermore, nanoemulsification significantly improved the permeation flux of curcumin from the hydrophilic matrix gel; the release kinetic of curcumin changed from zero order to a Higuchi release profile. Overall, the developed nanoemulsion system not only improved curcumin permeability but also protected the curcumin from chemical degradation.     

生育酚对亚麻籽油纳米乳液稳定性的影响

研究生育酚对亚麻籽油纳米乳液物理稳定性和氧化稳定性的影响。结果表明,生育酚会显著降低亚麻籽油纳米乳液中脂质氧化产物含量,进而提高乳液的氧化稳定性,同时不会影响乳液的粒径、PDI和Zeta电位。因此,生育酚可以作为抗氧化剂,改善亚麻籽油纳米乳液的氧化稳定性,但对乳液的物理稳定性无影响。     

Development and Evaluation of Repurposed Etoricoxib Loaded Nanoemulsion for Improving Anticancer Activities against Lung Cancer Cells

In the present work, novel modality for lung cancer intervention has been explored. Primary literature has established the potential role of cyclooxygenase-2 (COX-2) inhibitor in regression of multiple forms of carcinomas. To overcome its poor water solubility and boost anticancer activity, etoricoxib (ETO) was chosen as a therapeutic candidate for repurposing and formulated into a nanoemulsion (NE). The prepared ETO loaded NE was characterized for the surface charge, droplet size, surface morphology, and in vitro release. The optimized ETO loaded NE was then investigated for its anticancer potential employing A549 lung cancer cell line via cytotoxicity, apoptotic activity, mitochondrial membrane potential activity, cell migration assay, cell cycle analysis, Caspase-3, 9, and p53 activity by ELISA and molecular biomarker analysis through RT-PCR test. The developed ETO-NE formulation showed adequate homogeneity in the droplet size distribution with polydispersity index (PDI) of (0.2 ± 0.03) and had the lowest possible droplet size (124 ± 2.91 nm) and optimal negative surface charge (−8.19 ± 1.51 mV) indicative of colloidal stability. The MTT assay results demonstrated that ETO-NE exhibited substantial anticancer activity compared to the free drug. The ETO-NE showed a substantially potent cytotoxic effect against lung cancer cells, as was evident from the commencement of apoptosis/necrotic cell death and S-phase cell cycle arrests in A549 cells. The study on these molecules through RT-PCR confirmed that ETO-NE is significantly efficacious in mitigating the abundance of IL-B, IL-6, TNF, COX-2, and NF-kB as compared to the free ETO and control group. The current study demonstrates that ETO-NE represents a feasible approach that could provide clinical benefits for lung cancer patients in the future.     

纳米乳涂膜和1-甲基环丙烯处理对枇杷果实保鲜效果的影响

以‘白砂’枇杷果实为实验材料,以清水处理为对照,研究了纳米涂膜保鲜剂（nanoemulsion coating,NC）-1处理、1-甲基环丙烯（1-methylcyclopropene,1-MCP）处理、NC-1＋1-MCP处理对枇杷在低温（4 ℃）贮藏30 d过程中品质和生理代谢的影响。结果表明：NC-1＋1-MCP处理对枇杷的贮藏品质保持效果最佳,除VC含量外,贮藏结束时,该组果实硬度、腐烂率、质量损失率都显著低于其他处理组,且NC-1＋1-MCP处理更显著抑制了枇杷在贮藏过程中苯丙氨酸解氨酶的活力,从而抑制了木质素的积累;同时抑制了多酚氧化酶和过氧化物酶的活力,从而延缓了果实的褐变衰老。研究结果表明,相比于单一的NC-1或1-MCP处理,NC-1＋1-MCP处理对枇杷保鲜效果更好。     

均质工艺对制备鱼油微胶囊结构和理化性质的影响

本实验分别利用高压均质、空化射流和超声破碎3 种均质方式制备以大豆分离蛋白和磷脂酰胆碱包裹的鱼油纳米乳液和微胶囊,并对纳米乳液粒径、Zeta-电位、稳定性、黏度、乳化产率及微胶囊形貌、理化性质、稳定性进行比较分析,研究均质工艺对鱼油纳米乳液和微胶囊理化性质的影响。结果发现,空化射流工艺制备的纳米乳液平均粒径小,乳化产率和乳液稳定性较高,经过空化射流10 min制备的微胶囊包埋率达87.44%,溶解度较高,微胶囊颗粒表面形态饱满、致密、无裂纹和空隙,氧化稳定性和热稳定性较好。高压均质和超声破碎制得的纳米乳液平均粒径大,乳化产率和乳液稳定性较低,经过100 MPa高压均质和400 W超声破碎制得的微胶囊包埋率分别为80.36%和78.64%,溶解度相较于空化射流差,微胶囊颗粒表面分别出现微孔和较大的孔洞,氧化稳定性和热稳定性较差。傅里叶变换红外光谱分析结果表明3 种均质工艺均有较好的包埋效果。通过实验可以得出空化射流均质工艺制备的鱼油纳米乳液及微胶囊在产品性能上要优于其他两种均质工艺。本研究可为鱼油纳米乳液和微胶囊产品的均质工艺选择以及应用评价体系的构建提供理论依据。     

大分子乳化剂稳定的纳米乳中β-胡萝卜素的降解

分别以乳清分离蛋白、热处理乳清分离蛋白、乳清分离蛋白与麦芽糖糊精的混合物和美拉德反应复合物为乳化剂,制备β-胡萝卜素纳米乳,并考察其乳滴粒径分布及β-胡萝卜素的降解。结果表明：乳清分离蛋白与麦芽糖糊精共价复合后,形成的纳米乳液平均粒径更小,但复合物加速纳米乳中β-胡萝卜素的降解。而热处理乳清分离蛋白能显著抑制纳米乳中β-胡萝卜素的降解,其机制可能是蛋白质大分子聚集体的形成对β-胡萝卜素起保护作用。     

Self‐Degradable Lipid‐Like Materials Based on “Hydrolysis accelerated by the intra‐Particle Enrichment of Reactant (HyPER)” for Messenger RNA Delivery

RNA‐based therapeutics is a promising approach for curing intractable diseases by manipulating various cellular functions. For eliciting RNA (i.e., mRNA and siRNA) functions successfully, the RNA in the extracellular space must be protected and it must be delivered to the cytoplasm. In this study, the development of a self‐degradable lipid‐like material that functions to accelerate the collapse of lipid nanoparticles (LNPs) and the release of RNA into cytoplasm is reported. The self‐degradability is based on a unique reaction “Hydrolysis accelerated by intra‐Particle Enrichment of Reactant (HyPER).” In this reaction, a disulfide bond and a phenyl ester are essential structural components: concentrated hydrophobic thiols that are produced by the cleavage of the disulfide bonds in the LNPs drive an intraparticle nucleophilic attack to the phenyl ester linker, which results in further degradation. An oleic acid‐scaffold lipid‐like material that mounts all of these units (ssPalmO‐Phe) shows superior transfection efficiency to nondegradable or conventional materials. The insertion of the aromatic ring is unexpectedly revealed to contribute to the enhancement of endosomal escape. Since the intracellular trafficking is a sequential process that includes cellular uptake, endosomal escape, the release of mRNA, and translation, the improvement in each process synergistically enhances the gene expression.