作者承认为使研究成为可能沙特资助的奖学金（I821）。作者感谢显威刘博士在克兰菲尔德大学的TEM分析专家的支持。

1.油包水乳液的制备<ol><li>称重硬脂酸棕榈酸甘油酯（120毫克），肉豆蔻酸异丙酯（60毫克）中，d-α生育酚聚乙二醇琥珀酸酯（30毫克）和大豆卵磷脂（30毫克），并把它们添加到12.5毫升有机溶剂（6.25毫升丙酮和6.25毫升乙醇）。在该温度70℃（5℃固体脂质的熔点以上）的水浴迅速溶解该混合物。 </li><li>添加任一125，250或375毫克泊洛沙姆188的在12.5 DDH 2 O的毫升实现泊洛沙姆188溶液，这是受在与上述相同的温度下加热（分别）1-3％。 </li><li>从步骤1.2至来自步骤1.1的溶液的油相溶液中添加水相溶液在400rpm以形成磁力搅拌下乳剂。搅拌该乳液以400rpm再进行4小时，使有机溶剂蒸发。 </li></ol> 2.固化和同质化<ol><li>离开ŧ他乳剂在冷室（4℃）2小时，以固化/结晶。 </li><li>为了获得NLC，若使乳液纯粹的高分散（HSD）用一均在10,000-15,000转10-40分钟。 </li></ol> 3. NLC制备优化<ol><li>采取从步骤2.2样品在10000 15000和20000转的速度1,2和3％经受HSD的表面活性剂浓度，分别为10，20，30和40分钟的时间间隔，分别</li><li>检查粒度（PS），聚分散指数（PDI），形态和超微结构20的样品。 注:产生具有最小尺寸（155纳米）和PDI（0.2）值的颗粒被确定为最佳参数。 </li></ol> 4.准备DAC加载NLC的（NLC-DAC） <ol><li>如在水浴将混合物在70℃溶解之前加入DAC（70毫克）的在步骤1.1中所述制备的油相溶液。 </li><li> P如在步骤1.2和1％的表面活性剂描述repare水相溶液，并加入该溶液至该准备在步骤4.1中滴加在400rpm以形成磁力搅拌下的乳液。搅拌另外4小时，该乳液以蒸发有机溶剂。 </li><li>离开该乳液在冷室（4℃）2小时，以固化/如在步骤2中所述结晶，最后，若使乳液使用在步骤3中确定的最佳参数高剪切分散（HSD）。 </li></ol>

<ol>
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作者什么都没有透露。

基于脂质的纳米颗粒已被用于递送疏水性药物提供高度亲脂性载体。一个NLC是第二代固体脂质纳米结构载体，其在室温和体温固体。固体脂质掺入在NLC结果的液体脂质中一个不太完美结晶，从而增加了药物装载效率和也减少储存期间包封药物的驱逐。 为NLC合成中，最常用的方法包括油包水乳化，均质和固化/结晶21,22。均质化可以联络委员会到在水相中完全分散，同时...

达卡巴嗪（DAC）是施加通过核酸甲基化或直接DNA损伤的抗肿瘤活性，从 ​​而导致细胞周期停滞和细胞死亡1烷化剂。 作为第一线化疗剂，DAC已单独或与其它化疗药物用于治疗各种癌症2-6组合使用。它是用于治疗皮肤和转移性黑色素瘤，这是皮肤癌3,7,8的最积极的形式迄今使用的最活性剂。的响应速度，但是，只有20％在最好的，并且治疗效果往往伴随着严重的全身性副作用。 在其天然形式中，DAC是亲水性的并且是不稳定的，由于其光敏性9。临床使用的唯一可用的式目前是在悬浮液用于静脉内输注7,8所用的无菌粉末。低响应速度和高的全身毒性ř吃的药物，主要是由于其水溶性较差，因此低可用性目标在现场，和高配的非靶部位，从而限制了药物10的最大剂量。静脉入院耐药性的发展一起后快速降解和代谢限制临床应用和药物11的治疗效果。因此，迫切需要开发替代DAC制剂用于治疗恶性黑色素瘤。 含有脂质体的胶体体系，胶束或纳米颗粒已经集中研究了其在药物递送中使用如由Marilene 等人 12纳米粒子作为潜在药物载体已被吸引在过去十年中越来越多的关注，因为它们增加载药量的能力审查效率，控制药物释放，提高药物的药代动力学和生物分布，并由此计算的r-得出药全身毒性13。只有少数nanoformulations然而，迄今已对DAC递送研究，表示从相片变性药，增加药物溶解度的保护，以及改进的治疗效果10,14,15。然而，这些制剂有些还使用的是不符合成本效益的合成聚合物的纳米颗粒封装低效率受到影响。 纳米结构的脂质载体（NLC）由固体和液体脂质的混合物，已经开发了用于药物递送16,17。待包封的药物通常可溶于所述液体脂质和固体脂质相18，导致高的负荷和控制释放19。本研究旨在开发基于使用棕榈酸甘油酯和肉豆蔻酸异丙酯脂类NLC封装一个新的DAC配方。制备涉及油包水乳液，蒸发，凝固，和homogenizatioñ。该制剂已被表征为NLC尺寸，形状，超微结构，和分散度，药物包封率和药物负载20。

<table><tbody><tr><td>Dacarbazine (DAC)</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>D2390-100MG</td><td>drug used for uploading</td></tr><tr><td>glyceryl palmitostearate&amp;nbsp;</td><td>Gattefoss&amp;eacute; (Saint_Priest_c&amp;eacute;dex, France)</td><td>85251-77-0</td><td>solid lipid&amp;nbsp;</td></tr><tr><td>d-&amp;alpha;- Tocopherol polyethylene glycol succinate (TPGS)</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>57668</td><td>lipid phase surfactant</td></tr><tr><td>Poloxamer 188</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>15759-1KG</td><td>liqiud phase surfactant</td></tr><tr><td>Acetone&amp;nbsp;</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>650501-1L</td><td>organic solvent</td></tr><tr><td>Ethanol&amp;nbsp;</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>459836-1L</td><td>organic solvent</td></tr><tr><td>Soybean lecithin (SL)</td><td>Cuisine Innovation (Dijon, France)</td><td>SLL1402</td><td>lipid phase surfactant</td></tr><tr><td>Double-distilled water was collected in our laboratory from</td><td>Millipore-Q Gradient A10 ultra-pure water system (Millipore, France)</td><td>SAS - 67120&amp;nbsp;</td><td>aqueous phase&amp;nbsp;</td></tr><tr><td>T 25 digital ULTRA-TURRAX</td><td>IKA</td><td>3725000</td><td>as high shear disperser</td></tr><tr><td>Hotplate Magnetic Stirrer</td><td>Scientific Support, Inc</td><td>1454&amp;nbsp;</td><td>emulsion homogenization</td></tr></tbody></table>

encapsulation of cancer therapeutic agent dacarbazine using nanostructured lipid carrier

在临床使用达卡巴嗪（DAC）的唯一配方是静脉内输注，呈现较差治疗特性由于在水溶液中药物的低分散度。为了克服这个，包括棕榈酸甘油酯和异丙基肉豆蔻酸酯的纳米结构的脂质载体（NLC）的开发，以封装DAC。具有受控尺寸联络委员会采用以下油包水乳状液的凝固的高剪切分散（HSD）来实现的。合成参数，包括表面活性剂浓度，速度和HSD的时间进行了优化，以实现与尺寸，多分散指数为155±10nm的ζ电位最小NLC，0.2±0.01，和-43.4±2毫伏，分别。最佳工艺参数也用于DAC加载NLC的准备。装有DAC所得NLC分别具有尺寸，多分散指数为190±10nm的ζ电位，0.2±0.01，和-43.5±1.2毫伏。该药物包封EFFICIENCY和载药量分别达到98％和14％。这是使用NLC的DAC封装的第一份报告，这意味着NLC可能是一个新的潜在的候选者作为药物载体，以提高DAC的治疗特性。

国家图书馆和国家图书馆-DAC采用棕榈酸甘油酯和肉豆蔻酸异丙酯使用不同的参数的筹备工作特点是PS，PDI，形态和超微结构20。各国联络委员会的PS和PDI分别为表面活性剂浓度，HSD速度和持续时间有关。作为判断PS和联络委员会的PDI，最好的结果是用表面活性剂的1％和15,000rpm的30分钟（ 图1A，B和C）一种纯粹的分散速度，因此这...

Watch this Scientific Journal Video about Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier at JoVE.com

Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier

对于纳米结构的脂质载体（NLC）的合成中最常用的方法包括油包水乳化，均质和凝固。这是由凝固后施加高剪切分散，实现与希望的尺寸，提高了药物包封和药物负载效率为达卡巴嗪传递一个潜在的载体NLC在这里进行修改。

使用纳米脂质载体癌症治疗剂，达卡巴嗪封装

The only formula of dacarbazine (Dac) in clinical use is intravenous infusion, presenting a poor therapeutic profile due to the low dispersity of the drug ...

encapsulation-cancer-therapeutic-agent-dacarbazine-using

Research

JoVE Journal

Chemistry

11.0K 次观看.  Cranfield University. 对于纳米结构的脂质载体（NLC）的合成中最常用的方法包括油包水乳化，均质和凝固。这是由凝固后施加高剪切分散，实现与希望的尺寸，提高了药物包封和药物负载效率为达卡巴嗪传递一个潜在的载体NLC在这里进行修改。 

视频: Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier

Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles

Photodynamic therapy (PDT) is a non-invasive and non-surgical method representing an attractive alternative choice for lung cancer treatment. Photosensitizers selectively accumulate in tumor tissue and lead to tumor cell death in the presence of oxygen and the proper wavelength of light.
To increase the therapeutic effect of PDT, we developed both photosensitizer- and anticancer agent-loaded lung cancer-targeted nanoparticles. Both enhanced permeability and retention (EPR) effect-based passive targeting and hyaluronic-acid-CD44 interaction-based active targeting were applied. CD44 is a well-known hyaluronic acid receptor that is often introduced as a biomarker of non-small cell lung cancer. 
In addition, a combination of PDT and chemotherapy is adopted in the present study. This combination concept may increase anticancer therapeutic effects and reduce adverse reactions. 
We chose hypocrellin B (HB) as a novel photosensitizer in this study. It has been reported that HB causes higher anticancer efficacy of PDT compared to hematoporphyrin derivatives1. Paclitaxel was selected as the anticancer drug since it has proven to be a potential treatment for lung cancer2. 
The antitumor efficacies of photosensitizer (HB) solution, photosensitizer encapsulated hyaluronic acid-ceramide nanoparticles (HB-NPs), and both photosensitizer- and anticancer agent (paclitaxel)-encapsulated hyaluronic acid-ceramide nanoparticles (HB-P-NPs) after PDT were compared both in vitro and in vivo. The in vitro phototoxicity in A549 (human lung adenocarcinoma) cells and the in vivo antitumor efficacy in A549 tumor-bearing mice were evaluated.
The HB-P-NP treatment group showed the most effective anticancer effect after PDT. In conclusion, the HB-P-NPs prepared in the present study represent a potential and novel photosensitizer delivery system in treating lung cancer with PDT.

Photodynamic therapy (PDT) is an alternative choice for lung cancer treatment. To increase the therapeutic effect of PDT, lung cancer-targeted nanoparticles combined with chemotherapy were developed. Both in vitro and in vivo anticancer efficacies of PDT with prepared nanoparticles were evaluated.

光动力疗法的抗癌功效肺癌靶向纳米粒子

Photodynamic therapy (PDT) is a non-invasive and non-surgical method representing an attractive alternative choice for lung cancer treatment. ...

科研

癌症研究

Facile Preparation of Internally Self-assembled Lipid Particles Stabilized by Carbon Nanotubes

We present a facile method to prepare nanostructured lipid particles stabilized by carbon nanotubes (CNTs). Single-walled (pristine) and multi-walled (functionalized) CNTs are used as stabilizers to produce Pickering type oil-in-water (O/W) emulsions. Lipids namely, Dimodan U and Phytantriol are used as emulsifiers, which in excess water self-assemble into the bicontinuous cubic Pn3m phase. This highly viscous phase is fragmented into smaller particles using a probe ultrasonicator in presence of conventional surfactant stabilizers or CNTs as done here. Initially, the CNTs (powder form) are dispersed in water followed by further ultrasonication with the molten lipid to form the final emulsion. During this process the CNTs get coated with lipid molecules, which in turn are presumed to surround the lipid droplets to form a particulate emulsion that is stable for months. The average size of CNT-stabilized nanostructured lipid particles is in the submicron range, which compares well with the particles stabilized using conventional surfactants. Small angle X-ray scattering data confirms the retention of the original Pn3m cubic phase in the CNT-stabilized lipid dispersions as compared to the pure lipid phase (bulk state). Blue shift and lowering of the intensities in characteristic G and G&#39; bands of CNTs observed in Raman spectroscopy characterize the interaction between CNT surface and lipid molecules. These results suggest that the interactions between the CNTs and lipids are responsible for their mutual stabilization in aqueous solutions. As the concentrations of CNTs employed for stabilization are very low and lipid molecules are able to functionalize the CNTs, the toxicity of CNTs is expected to be insignificant while their biocompatibility is greatly enhanced. Hence the present approach finds a great potential in various biomedical applications, for instance, for developing hybrid nanocarrier systems for the delivery of multiple functional molecules as in combination therapy or polytherapy.

We report on a smart application of carbon nanotubes for kinetic stabilization of lipid particles that contain self-assembled nanostructures in their cores. The preparation of lipid particles requires rather low concentrations of carbon nanotubes permitting their use in biomedical applications such as drug delivery.

内部自组装脂质颗粒的简易制备碳纳米管稳定

We present a facile method to prepare nanostructured lipid particles stabilized by carbon nanotubes (CNTs). Single-walled (pristine) and multi-walled ...

化学

Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect resulting in significant reductions in systemic toxicity. Nonetheless, insufficient release of encapsulated drug from liposomes has limited their clinical efficacy. Temperature-sensitive liposomes have been engineered to provide site-specific release of drug in order to overcome the problem of limited tumor drug bioavailability. Our lab has designed and developed a heat-activated thermosensitive liposome formulation of cisplatin (CDDP), known as HTLC, to provide triggered release of CDDP at solid tumors. Heat-activated delivery in vivo was achieved in murine models using a custom-built laser-based heating apparatus that provides a conformal heating pattern at the tumor site as confirmed by MR thermometry (MRT). A fiber optic temperature monitoring device was used to measure the temperature in real-time during the entire heating period with online adjustment of heat delivery by alternating the laser power. Drug delivery was optimized under magnetic resonance (MR) image guidance by co-encapsulation of an MR contrast agent (i.e.,&#160;gadoteridol) along with CDDP into the thermosensitive liposomes as a means to validate the heating protocol and to assess tumor accumulation. The heating protocol consisted of a preheating period of 5 min prior to administration of HTLC and 20 min heating post-injection. This heating protocol resulted in effective release of the encapsulated agents with the highest MR signal change observed in the heated tumor in comparison to the unheated tumor and muscle. This study demonstrated the successful application of the laser-based heating apparatus for preclinical thermosensitive liposome development and the importance of MR-guided validation of the heating protocol for optimization of drug delivery.

AN MRI-compatible&#160;custom-designed laser-based heating apparatus has been developed to provide local heating of subcutaneous tumors in order to activate release of agents from thermosensitive liposomes specifically at the tumor region.

定制设计的基于激光的加热装置顺铂触发释放的热敏脂质体与磁共振成像制导

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect ...

生物工程

Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles

Micelles have been successfully used for the delivery of anticancer drugs. Amphiphilic polymers form core-shell structured micelles in an aqueous environment through self-assembly. The hydrophobic core of micelles functions as a drug reservoir and encapsulates hydrophobic drugs. The hydrophilic shell prevents the aggregation of micelles and also prolongs their systemic circulation in vivo. In this protocol, we describe a method to synthesize a doxorubicin lipophilic pro-drug, doxorubicin-palmitic acid (DOX-PA), which will enhance drug loading into micelles. A pH-sensitive hydrazone linker was used to conjugate doxorubicin with the lipid, which facilitates the release of free doxorubicin inside cancer cells. Synthesized DOX-PA was purified with a silica gel column using dichloromethane/methanol as the eluent. Purified DOX-PA was analyzed with thin layer chromatography (TLC) and 1H-Nuclear Magnetic Resonance Spectroscopy (1H-NMR). A film dispersion method was used to prepare DOX-PA loaded DSPE-PEG micelles. In addition, several methods for characterizing micelle formulations are described, including determination of DOX-PA concentration and encapsulation efficiency, measurement of particle size and distribution, and assessment of in vitro anticancer activities. This protocol provides useful information regarding the preparation and characterization of drug-loaded micelles and thus will facilitate the research and development of novel micelle-based cancer nanomedicines.

A protocol for the preparation and characterization of lipophilic doxorubicin pro-drug loaded 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG) micelles is described.

制备和表征亲脂阿霉素前药胶束

Micelles have been successfully used for the delivery of anticancer drugs. Amphiphilic polymers form core-shell structured micelles in an aqueous ...

Phase Change Dimethyldioctadecylammonium-Shelled Microdroplets as a Promising Drug Delivery System: Results on 3D Spheroids of Mammalian Tumor Cells

Significant improvement of phase-change perfluorocarbon microdroplets (MDs) in the vast theranostic scenario passes through the optimization of the MDs composition with respect to synthesis efficiency, stability, and drug delivery capability. To this aim, decafluoropentane (DFP) MDs stabilized by a shell of dimethyldioctadecylammonium bromide (DDAB) cationic surfactant were designed. A high concentration of DDAB-MDs was readily obtained within a few seconds by pulsed high-power insonation, resulting in low polydisperse 1 &#181;m size droplets. Highly positive &#950;-potential, together with a long, saturated hydrocarbon chains of the DDAB shell, are key factors to stabilize the droplet and the drug cargo therein. The high affinity of the DDAB shell with cell plasma membrane allows for localized chemotherapeutics delivery by increasing the drug concentration at the tumor cell interface and boosting the uptake. This would turn DDAB-MDs into a relevant drug delivery tool exhibiting high antitumor activity at very low drug doses.
In this work, the efficacy of such an approach is shown to dramatically improve the effect of doxorubicin against 3D spheroids of mammalian tumor cells, MDA-MB-231. The use of&#160;three-dimensional (3D) cell cultures developed in the form of multicellular tumor spheroids (i.e., densely packed cells in a spherical shape) has numerous advantages compared to 2D cell cultures: in addition to have the potential to bridge the gap between conventional in vitro studies and animal testing, it will improve the ability to perform more predictive in vitro screening assays for preclinical drug development or evaluate the potential of off-label drugs and new co-targeting strategies.

Decafluoropentane microdroplets developed with a shell of dimethyldioctadecylammonium bromide exhibited an exceptional colloidal stability and an actractive biointerface. DDAB-MDs proved to be efficient drug reservoirs characterized by a high affinity to plasma membranes together with enhanced uptake and antitumor activity of Doxorubicin against human triple-negative breast cancer (MDA-MB-231) 3D model.

Significant improvement of phase-change perfluorocarbon microdroplets (MDs) in the vast theranostic scenario passes through the optimization of the MDs ...

Targeted Plasma Membrane Delivery of a Hydrophobic Cargo Encapsulated in a Liquid Crystal Nanoparticle Carrier

The controlled delivery of drug/imaging agents to cells is critical for the development of therapeutics and for the study of cellular signaling processes. Recently, nanoparticles (NPs) have shown significant promise in the development of such delivery systems. Here, a liquid crystal NP (LCNP)-based delivery system has been employed for the controlled delivery of a water-insoluble dye, 3,3&#8242;-dioctadecyloxacarbocyanine perchlorate (DiO), from within the NP core to the hydrophobic region of a plasma membrane bilayer. During the synthesis of the NPs, the dye was efficiently incorporated into the hydrophobic LCNP core, as confirmed by multiple spectroscopic analyses. Conjugation of a PEGylated cholesterol derivative to the NP surface (DiO-LCNP-PEG-Chol) enabled the binding of the dye-loaded NPs to the plasma membrane in HEK 293T/17 cells. Time-resolved laser scanning confocal microscopy and F&#246;rster resonance energy transfer (FRET) imaging confirmed the passive efflux of DiO from the LCNP core and its insertion into the plasma membrane bilayer. Finally, the delivery of DiO as a LCNP-PEG-Chol attenuated the cytotoxicity of DiO; the NP form of DiO exhibited ~30-40% less toxicity compared to DiOfree delivered from bulk solution. This approach demonstrates the utility of the LCNP platform as an efficient modality for the membrane-specific delivery and modulation of hydrophobic molecular cargos.

A liquid crystal nanoparticle (LCNP) nanocarrier is exploited as a vehicle for the controlled delivery of a hydrophobic cargo to the plasma membrane of living cells.

疏水货物封装有针对性的质膜交付在液晶纳米颗粒载体

The controlled delivery of drug/imaging agents to cells is critical for the development of therapeutics and for the study of cellular signaling processes. ...

Formulation and Characterization of Bioactive Agent Containing Nanodisks

The term nanodisk refers to a discrete type of nanoparticle comprised of a bilayer forming lipid, a scaffold protein, and an integrated bioactive agent. Nanodisks are organized as a disk-shaped lipid bilayer whose perimeter is circumscribed by the scaffold protein, usually a member of the exchangeable apolipoprotein family. Numerous hydrophobic bioactive agents have been efficiently solubilized in nanodisks by their integration into the hydrophobic milieu of the particle&#39;s lipid bilayer, yielding a largely homogenous population of particles in the range of 10-20 nm in diameter. The formulation of nanodisks requires a precise ratio of individual components, an appropriate sequential addition of each component, followed by bath sonication of the formulation mixture. The amphipathic scaffold protein spontaneously contacts and reorganizes the dispersed bilayer forming lipid/bioactive agent mixture to form a discrete, homogeneous population of nanodisk&#160;particles. During this process, the reaction mixture transitions from an opaque, turbid appearance to a clarified sample that, when fully optimized, yields no precipitate upon centrifugation. Characterization studies involve the determination of bioactive agent solubilization efficiency, electron microscopy, gel filtration chromatography, ultraviolet visible (UV/Vis) absorbance spectroscopy, and/or fluorescence spectroscopy. This is normally followed by an investigation of biological activity using cultured cells or mice. In the case of nanodisks harboring an antibiotic (i.e., the macrolide polyene antibiotic amphotericin B), their ability to inhibit the growth of yeast or fungi as a function of concentration or time can be measured. The relative ease of formulation, versatility with respect to component parts, nanoscale particle size, inherent stability, and aqueous solubility permits myriad in vitro and in vivo applications of nanodisk technology. In the present article, we describe a general methodology to formulate and characterize nanodisks containing amphotericin&#160;B as the hydrophobic bioactive agent.

Here, we describe the production and characterization of bioactive agents containing nanodisks. Amphotericin B nanodisks are taken as an example to describe the protocol in a stepwise manner.

含纳米片生物活性剂的配制与表征

The term nanodisk refers to a discrete type of nanoparticle comprised of a bilayer forming lipid, a scaffold protein, and an integrated bioactive agent. ...

生物化学

Uptake of New Lipid-coated Nanoparticles Containing Falcarindiol by Human Mesenchymal Stem Cells

Nanoparticles are the focus of an increased interest in drug delivery systems for cancer therapy. Lipid-coated nanoparticles are inspired in structure and size by low-density lipoproteins (LDLs) because cancer cells have an increased need for cholesterol to proliferate, and this has been exploited as a mechanism for delivering anticancer drugs to cancer cells. Moreover, depending on drug chemistry, encapsulating the drug can be advantageous to avoid degradation of the drug during circulation in vivo. Therefore, in this&#160;study, this design is used to fabricate lipid-coated nanoparticles of the anticancer drug falcarindiol, providing a potential new delivery system of falcarindiol in order to stabilize its chemical structure against degradation and improve its uptake by tumors. Falcarindiol nanoparticles, with a phospholipid and cholesterol monolayer encapsulating the purified drug core of the particle, were designed. The lipid monolayer coating consists of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol (Chol), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE PEG 2000) along with the fluorescent label DiI (molar ratios of 43:50:5:2). The nanoparticles are fabricated using the rapid injection method, which is a fast and simple technique to precipitate nanoparticles by good-solvent for anti-solvent exchange. It consists of a rapid injection of an ethanol solution containing the nanoparticle components into an aqueous phase. The size of the fluorescent nanoparticles is measured using dynamic light scattering (DLS) at 74.1 &#177; 6.7 nm. The uptake of the nanoparticles is tested in human mesenchymal stem cells (hMSCs) and imaged using fluorescence and confocal microscopy. The uptake of the nanoparticles is observed in hMSCs, suggesting the potential for such a stable drug delivery system for falcarindiol.

This article describes the encapsulation of falcarindiol in lipid-coated 74 nm nanoparticles. The cellular uptake of the nanoparticles&#160;by human stem cells into lipid droplets is monitored by fluorescent and confocal imaging. Nanoparticles are fabricated by the rapid injection method of solvent shifting, and their size is measured with the dynamic light scattering technique.

人骨髓间充质干细胞吸收含有法卡林多醇的新型脂质包覆纳米颗粒

Nanoparticles are the focus of an increased interest in drug delivery systems for cancer therapy. Lipid-coated nanoparticles are inspired in structure and ...

Preparation and Characterization of Nanoliposomes for the Entrapment of Bioactive Hydrophilic Globular Proteins

Liposome nanocapsules have been applied for many purposes in the pharmaceutical, cosmetic, and food industries. Attributes of liposomes include their biocompatibility, biodegradability, non-immunogenicity, non-toxicity, and ability to entrap both hydrophilic and hydrophobic compounds. The classical hydration of thin lipid films in an organic solvent is applied herein as a technique to encapsulate tarin, a plant lectin, in nanoliposomes. Nanoliposome size, stability, entrapment efficiency, and morphological characterization are described in detail. The nanoliposomes are prepared using 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine (DOPE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (ammonium salt; DSPE-MPEG 2000), and cholesterylhemisuccinate (CHEMS) as the main constituents. Lipids are first dissolved in chloroform to obtain a thin lipid film that is subsequently rehydrated in ammonium sulfate solution containing the protein to be entrapped and incubated overnight. Then, sonication and extrusion techniques are applied to generate nanosized unilamellar vesicles. The size and polydispersity index of the nanovesicles are determined by dynamic light scattering, while nanovesicle morphology is assessed by scanning electron microscopy. Entrapment efficiency is determined by the ratio of the amount of unencapsulated protein to original amount of initially loaded protein. Homogeneous liposomes are obtained with an average size of 155 nm and polydispersity index value of 0.168. A high entrapment efficiency of 83% is achieved.

This study describes classical hydration using the thin lipid film method for nanoliposome preparation followed by nanoparticle characterization. A 47 kDa-hydrophilic and globular protein, tarin, is successfully encapsulated as a strategy to improve stability, avoid fast clearance, and promote controlled release. The method can be adapted to hydrophobic molecules encapsulation.

生物活性亲水球状蛋白的纳米脂质体制备与表征

Liposome nanocapsules have been applied for many purposes in the pharmaceutical, cosmetic, and food industries. Attributes of liposomes include their ...

Using In Vitro Live-cell Imaging to Explore Chemotherapeutics Delivered by Lipid-based Nanoparticles

Conventional imaging techniques can provide detailed information about cellular processes. However, this information is based on static images in an otherwise dynamic system, and successive phases are easily overlooked or misinterpreted. Live-cell imaging and time-lapse microscopy, in which living cells can be followed for hours or even days in a more or less continuous fashion, are therefore very informative. The protocol described here allows for the investigation of the fate of chemotherapeutic nanoparticles after the delivery of doxorubicin (dox) in living cells. Dox is an intercalating agent that must be released from its nanocarrier to become biologically active. In spite of its clinical registration for more than two decades, its uptake, breakdown, and drug release are still not fully understood. This article explores the hypothesis that lipid-based nanoparticles are taken up by the tumor cells and are slowly degraded. Released dox is then translocated to the nucleus. To prevent fixation artifacts, live-cell imaging and time-lapse microscopy, described in this experimental procedure, can be applied.