TG-DHA高含量脱腥鱼油对脂代谢的调节作用

目的：探究TG-DHA高含量脱腥鱼油的制备及对高脂饮食小鼠脂代谢的调节作用。方法：脂质体包埋技术制备TG-DHA高含量脱腥鱼油。将雄性C57BL/6J小鼠（6周龄）随机分为对照组（C）、模型组（M）、TG-DHA高含量鱼油组（O-DHA）、TG-DHA高含量脱腥鱼油组（L-DHA）。连续灌胃8周后,检测小鼠血清、肝脏脂质水平;测定肝脏脂代谢相关基因脂肪酸合成酶（Fatty acid synthase,FAS）、固醇调节元件结合蛋白1c （Sterol regulatory element binding protein-1c,SREBP-1c）、肉碱棕榈酰转移酶1（Carnitine palmitoyl transferase,CPT1）、脂蛋白脂酶（Lipoprotein lipase,LPL） mRNA表达量。结果：脂质体包埋掩盖了己醛、2,4-庚二烯醛等鱼油中的腥味物质。TG-DHA高含量脱腥鱼油中的DHA含量为73.74%,粒径为159.50 nm,Zeta电位为-43.10 mV,稳定性良好,且在动物体内易于被消化吸收。L-DHA可显著改善高脂饮食小鼠血清和肝脏脂质水平（P<0.05）,O-DHA可显著改善高脂饮食小鼠血清水平和肝脏中的TG含量（P<0.05）,二者均能极显著降低FAS mRNA表达（P<0.01）,显著上调CPT1 mRNA表达（P<0.05）,且L-DHA效果更好。结论：TG-DHA高含量脱腥鱼油可改善高脂饮食导致的脂代谢紊乱,其机制与下调肝脏脂肪酸合成,促进脂肪酸分解代谢有关。     

多囊泡型二氢杨梅素脂质体的制备、表征及其抑菌性能

耐药金色葡萄球菌的出现和高效抗生素的缺乏已经对食品质量与公共安全造成威胁,因此,亟需寻找一种新的治疗策略来应对日益严峻的细菌挑战。本研究采用水热提取法从藤茶提取二氢杨梅素（DMY）,并以脂质体为药物载体、聚乙二醇4000为修饰剂成功制备出多囊泡型二氢杨梅素脂质体（DMY-lips）。使用紫外分光光度计、傅里叶红外光谱仪、X射线粉末衍射仪和同步热分析仪分析确定了DMY的成功包覆,并通过透射电子显微镜和纳米粒度测试仪证实了脂质体的多囊泡结构。该脂质体粒径均一,平均粒径为155 nm,载药率为42.93%。此外,抑菌实验证实脂质体的包覆提高了DMY的抑菌活性和抑菌时间,这主要是由于脂质体提高了DMY的水解度和膜渗透度。DMY-lips对金色葡萄球菌的最小抑菌浓度为0.05 mg/ml。生物扫描电镜和电导率测试实验表明DMY-lips可以破坏金色葡萄球菌的细胞壁和细胞膜,导致菌体膜内内容物流出而死亡。因此,该多囊泡型二氢杨梅素脂质体在制药行业具有巨大潜力,并有望缓解医疗系统对化学抗生素的依赖。     

Insights into the Action Mechanism of the Antimicrobial Peptide Lasioglossin III

Lasioglossin III (LL-III) is a cationic antimicrobial peptide derived from the venom of the eusocial bee Lasioglossum laticeps. LL-III is extremely toxic to both Gram-positive and Gram-negative bacteria, and it exhibits antifungal as well as antitumor activity. Moreover, it shows low hemolytic activity, and it has almost no toxic effects on eukaryotic cells. However, the molecular basis of the LL-III mechanism of action is still unclear. In this study, we characterized by means of calorimetric (DSC) and spectroscopic (CD, fluorescence) techniques its interaction with liposomes composed of a mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-rac-phosphoglycerol (POPG) lipids as a model of the negatively charged membrane of pathogens. For comparison, the interaction of LL-III with the uncharged POPC liposomes was also studied. Our data showed that LL-III preferentially interacted with anionic lipids in the POPC/POPG liposomes and induces the formation of lipid domains. Furthermore, the leakage experiments showed that the peptide could permeabilize the membrane. Interestingly, our DSC results showed that the peptide-membrane interaction occurs in a non-disruptive manner, indicating an intracellular targeting mode of action for this peptide. Consistent with this hypothesis, our gel-retardation assay experiments showed that LL-III could interact with plasmid DNA, suggesting a possible intracellular target.     

Comparison of different separative techniques in the quantitative determination of active compound enclosed in liposomal systems

The suitability of three different separative techniques, dialysis, gel filtration and centrifugation, for determining the percentage of active compound included (PAI) in liposomal systems was assessed. Two model compounds, glucose and vitamin E acetate were encapsulated in dipalmitoylphosphatidylcholine (DPPC), soybean lecithin (SL) and hydrogenated soybean lecithin (HSL) multilamellar vesicles (MLV). Vitamin E acetate PAI values from DPPC MLV liposomes obtained by dialysis, gel filtration and centrifugation, were compared with those determined by differential scanning calorimetry. Glucose PAI values from DPPC MLV liposomes, obtained using the same separative techniques, were compared with that calculated by taking into account the glucose content of the liposome internal aqueous phase on the basis of liposome mean size determined by light scattering.
Vitamin E acetate and glucose PAI values from SL and HSL liposomes were compared with those obtained for DPPC liposomes. Dialysis proved suitable for PAI determination for both lipophilic and hydrophilic compounds, centrifugation was found to be suitable only for the determination of lipophilic compound PAI values while gel filtration using Sephadex G-25M proved inadequate for the determination of PAI values for both lipophilic and hydrophilic compounds in the experimental conditions used in this study.     

植物甾醇油酸酯-虾青素复合脂质体的制备工艺优化

为了改善虾青素的水溶性和稳定性,探索植物甾醇酯用于构建负载虾青素脂质体的可行性,以大豆磷脂为主要膜材,采用薄膜-超声法制备植物甾醇油酸酯-虾青素复合脂质体(L-PA)。以包封率为评价指标,通过单因素试验和Box-Behnken响应面试验优化L-PA的制备工艺。结果表明：L-PA制备的最佳工艺条件为植物甾醇油酸酯与大豆磷脂质量比1∶10、磷酸盐缓冲液pH 7.4、超声时间4 min、吐温80与大豆磷脂质量比1∶2、有机相与水相体积比1∶4、虾青素与大豆磷脂质量比1∶50,在此条件下L-PA的包封率为95.24%。因此,植物甾醇油酸酯可用于构建负载虾青素的脂质体。     

Specific surface modification of liposomes for gut targeting of food bioactive agents

Liposomes have become a research hotspot in recent years as food delivery systems with attractive properties, including the bilayer structure assembled like the cell membrane, reducing the side-effect and improving environmental stability of cargos, controlling release, extending duration of functional ingredients, and high biodegradable and biocompatible abilities in the body. However, the conventional liposomes lack stability during storage and are weak in targeted absorption in the gastrointestinal track. At present, surface modification has been approved to be an effective platform to shield these barricades and help liposomes deliver the agents safely and effectively to the ideal site. In this review, the gastrointestinal stability of conventional liposomes, cargo release models from liposomes, and the biological fate of the core materials after release were emphasized. Then, the strategies in both physical and chemical perspectives to improve the stability and utilization of liposomes in the gastrointestinal tract, and the emerging approaches for improving gut targeting by specifically modified liposomes and the intestinal receptors relative to liposomes/cargos absorption were highlighted. Last but not the least, the safety, challenges, and opportunities for the improvement of liposomal bioavailability were also discussed to inspire new applications of liposomes as oral carriers.     

Advancements and Challenges in Multidomain Multicargo Delivery Vehicles

Reparative and regenerative processes are well‐orchestrated temporal and spatial events that are governed by multiple cells, molecules, signaling pathways, and interactions thereof. Yet again, currently available implantable devices fail largely to recapitulate nature's complexity and sophistication in this regard. Herein, success stories and challenges in the field of layer‐by‐layer, composite, self‐assembly, and core–shell technologies are discussed for the development of multidomain/multicargo delivery vehicles.     

Modeling Interactions between Liposomes and Hydrophobic Nanosheets

2D nanomaterials could cause structural disruption and cytotoxic effects to cells, which greatly challenges their promising biomedical applications including biosensing, bioimaging, and drug delivery. Here, the physical and mechanical interaction between lipid liposomes and hydrophobic nanosheets is studied utilizing coarse‐grained (CG) molecular dynamics (MD) simulations. The simulations reveal a variety of characteristic interaction morphologies that depend on the size and the orientation of nanosheets. Dynamic and thermodynamic analyses on the morphologic evolution provide insights into molecular motions such as “nanosheet rotation,” “lipid extraction,” “lipid flip‐flop,” and “lipid spreading.” Driven by these molecular motions, hydrophobic nanosheets cause morphologic changes of liposomes. The lipid bilayer structure can be corrugated, and the overall liposome sphere can be split or collapsed by large nanosheets. In addition, nanosheets embedded into lipid bilayers greatly weaken the fluidity of lipids, and this effect can be cumulatively enhanced as nanosheets continuously intrude. These results could facilitate molecular‐level understanding on the cytotoxicity of nanomaterials, and help future nanotoxicology studies associating computational modeling with experiments.     

Poly(Sarcosine) Surface Modification Imparts Stealth‐Like Properties to Liposomes

Circulation lifetime is a crucial parameter for a successful therapy with nanoparticles. Reduction and alteration of opsonization profiles by surface modification of nanoparticles is the main strategy to achieve this objective. In clinical settings, PEGylation is the most relevant strategy to enhance blood circulation, yet it has drawbacks, including hypersensitivity reactions in some patients treated with PEGylated nanoparticles, which fuel the search for alternative strategies. In this work, lipopolysarcosine derivatives (BA‐pSar, bisalkyl polysarcosine) with precise chain lengths and low polydispersity indices are synthesized, characterized, and incorporated into the bilayer of preformed liposomes via a post insertion technique. Successful incorporation of BA‐pSar can be realized in a clinically relevant liposomal formulation. Furthermore, BA‐pSar provides excellent surface charge shielding potential for charged liposomes and renders their surface neutral. Pharmacokinetic investigations in a zebrafish model show enhanced circulation properties and reduction in macrophage recognition, matching the behavior of PEGylated liposomes. Moreover, complement activation, which is a key factor in hypersensitivity reactions caused by PEGylated liposomes, can be reduced by modifying the surface of liposomes with an acetylated BA‐pSar derivative. Hence, this study presents an alternative surface modification strategy with similar benefits as the established PEGylation of nanoparticles, but with the potential of reducing its drawbacks.