使用渗透压力调节聚酯聚合物的形状
Summary
聚合物体是自组装的聚合囊泡，形成球形，以尽量减少吉布的自由能量。在药物输送方面，更拉长的结构是有益的。本协议建立了方法，以创建更多的棒状聚合物体，与拉长的纵横比，使用盐诱导渗透压力和减少内部囊泡体积。
Abstract
聚合物体是膜结合的双层囊泡，由嗜血块共聚体制成，可以封装疏水和亲水有效载荷，用于药物输送应用。尽管聚合物体很有前途，但由于其球形，其应用有限，而细胞不易被细胞占据，固体纳米粒子科学家证明了这一点。本文描述了一种盐基方法，用于提高球形聚合物（乙二醇）（PEG）基聚合物的纵横比。这种方法可以拉长聚合物体，并最终通过在形成后透析中加入氯化钠来控制其最终形状。盐浓度可以多种多样，如本方法所述，基于用作聚合物和目标形状基础的块聚合物的疏水性。拉长的纳米粒子有可能更好地瞄准直径较大的血管中的内皮，如观察到边缘的静脉。本方案可利用拉长技术与聚合物的双载长循环效益配合，扩大治疗纳米粒子的应用。
Introduction
形状调制是改善纳米粒子介质药物输送的一种相对较新和有效的方法。形态的变化不仅增加了粒子的表面积，反过来又增加了承载能力，而且对提高稳定性、循环时间、生物可用性、分子靶向和受控释放1具有全面的影响。聚合物体是该方法中焦点的纳米粒子，它倾向于热力学自我组装成球形，这已被证明在细胞吸收中不切实际，并且更容易在免疫系统中作为异物检测到。能够将结构拉长成一根蛋白石或一根棒子，将使药物携带者通过模仿原生细胞来躲避巨噬细胞，并更成功地将它们交付到他们期望的目标2、3、4、5、6、7。聚合物体的显著优点，包括有效载荷的膜绑定保护，膜的刺激反应，以及亲水药物和疏水药物8，9，10的双重封装，使他们在形状调制过程中保持药物输送的有力候选者。
调节聚合物体的形状有许多不同的方法，每种方法都有各自的优缺点。然而，这些方法大多分为两类：溶剂驱动和盐驱动的渗透压力变化11。这两种方法都旨在克服聚合物形成球形平衡形状后存在的弯曲能量。通过引入渗透压力梯度，聚合物体可以被迫弯曲成拉长结构，尽管强弯曲能量11，12。
基于溶剂的方法探索形状的变化灵感来自金和范赫斯特13的工作。他们将有机溶剂和水混合物中的聚合物塑料化，将有机溶剂捕获在囊泡膜中，并将水从囊芯中排出。最终，粒子的内部体积如此之低，以至于拉长了。虽然这种方法已显示出希望，但它缺乏实用性。此方法需要不同的溶剂为每个单独的聚合物骨干参与调制。因此，它并不广泛适用于促进形状的变化。相反，盐基方法是均匀的，并利用一个通用驱动因素，可以引入渗透压力到许多块聚合物为基础的聚合物体。
该项目采用拉莫罗等人引进的盐基方法。此协议涉及两轮透析。一种旨在通过去除在生产过程中可能困在双层中的有机溶剂来净化和凝固聚（乙二醇）-b-聚合物（乳酸）（PEG-PLA）聚合物，另一种则促进形状变化。第二个透析步骤引入了 50 mM NaCl 溶液，可创建渗透压力梯度以驱动形状变化。这种方法得到了萨尔瓦等人的支持，他们指出，溶液中的超音速应激会导致囊泡收缩15。此方法基于先前发布的方法14， 从 50-200 m NaCl 中查看两种不同的聚酯聚合物和各种盐梯度。聚酯由于其生物相容性和生物降解而使用。盐梯度对形状有不同的影响，具体取决于块共聚体骨干的疏水性。它可用于创建前列腺、棒和豆类细胞。之所以选择这种盐驱动的方法，是因为复制的便利性和实验的多功能性。
Protocol
Representative Results
Discussion
自组装系统是出了名的无法控制。它们的最终属性，包括大小、形状和结构，是由所选的两栖动物的疏水特性和所选溶剂环境驱动的。嗜血块共聚物倾向于球形，从而最大限度地减少吉布的自由能量，并导致热力学平衡23，从而形成聚合物体。由于其平衡性质，聚合物体在拉长或改变形状方面具有更大的挑战性，因此，与固体纳米粒子相比，研究较少。溶剂驱动的方法已经与PEG-b…
Offenlegungen
The authors have nothing to disclose.
Acknowledgements
该项目部分由国家卫生研究院项目5P20GM103499-19通过学生启动研究项目项目资助。这项工作也得到了克莱姆森的创意调查计划的部分支持。我们也感谢尼古拉斯·拉莫罗和奥恩·阿里谁最初致力于创建这个协议，发表他们的第一篇论文引用这里14。
Materials
| 15*45 vials screw thread w/cap attached | Fisherbrand | 9609104000 | |
| Dimethyl Sulfoxide | Fisher Chemical | D128-1 | |
| Dimethyl Sulfoxide | BDH | BDH1115-1LP | |
| Isoremp stirrers, hotplates, and stirring hotplates | Fisher scientific | CIC00008110V19 | |
| LEGATO 130 SYRINGE PUMP | kd Scientific | 788130 | |
| PEG(1000)-b-PLA(5000), Diblock Polymer | Polysciences Inc | 24381-1 | note the molecular weights when replicating |
| Poly(ethylene glycol) (2000) Methyl ether-block-poly(lactide-co-glycolide) (4500) | Sigma aldrich | 764825-1G | note the molecular weights when replicating |
| Single-Use Syringe/BD PrecisionGlide Needle combination, sterile, BD medical | BD medical | BD305620 | Tuberculin |
| Sodium Chloride | BDH | BDH9286 | |
| Zetasizer Nano ZS | Malvern |
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