使用纳米脂质载体癌症治疗剂，达卡巴嗪封装
Summary
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。
Abstract
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。
Introduction
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。
Protocol
1.油包水乳液的制备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。 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?…
Representative Results
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…
Discussion
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…
Disclosures
The authors have nothing to disclose.
Acknowledgements
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。
Materials
| Dacarbazine (DAC) | Sigma Aldrich (Gillingham Dorset, UK) | D2390-100MG | drug used for uploading |
| glyceryl palmitostearate | Gattefossé (Saint_Priest_cédex, France) | 85251-77-0 | solid lipid |
| d-α- Tocopherol polyethylene glycol succinate (TPGS) | Sigma Aldrich (Gillingham Dorset, UK) | 57668 | lipid phase surfactant |
| Poloxamer 188 | Sigma Aldrich (Gillingham Dorset, UK) | 15759-1KG | liqiud phase surfactant |
| Acetone | Sigma Aldrich (Gillingham Dorset, UK) | 650501-1L | organic solvent |
| Ethanol | Sigma Aldrich (Gillingham Dorset, UK) | 459836-1L | organic solvent |
| Soybean lecithin (SL) | Cuisine Innovation (Dijon, France) | SLL1402 | lipid phase surfactant |
| Double-distilled water was collected in our laboratory from | Millipore-Q Gradient A10 ultra-pure water system (Millipore, France) | SAS – 67120 | aqueous phase |
| T 25 digital ULTRA-TURRAX | IKA | 3725000 | as high shear disperser |
| Hotplate Magnetic Stirrer | Scientific Support, Inc | 1454 | emulsion homogenization |
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Cite This Article
Almoussalam, M., Zhu, H. Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier. J. Vis. Exp. (110), e53760, doi:10.3791/53760 (2016).