Polymersomes in Polymersomes: Multiple Loading and Permeability Control
Polymersomes in Polymersomes: Multiple Loading and Permeability Control
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DOI：
10.1002/anie.201106410
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Lecommandoux, Sebastien
中科院分区：
文献类型：
--
作者：
Marguet, Maite;Edembe, Lise;Lecommandoux, Sebastien
聚合物囊泡聚合物囊泡是由两亲性嵌段共聚物在水溶液中通过自由能最小化自组装得到的囊泡。[1]它们作为药物递送系统，[2]传感器和/或纳米反应器[3]的潜在用途最近引起了极大的兴趣。[4]与脂质体相比，聚合物囊泡具有更大的机械稳定性和更低的渗透性，脂质体是其结构类似物，经常遭受过早的药物泄漏。[5]为了规避这种限制，Zasadzinski和同事开发了脂质体结构中的脂质体，也称为“囊泡体”。[6]在这种分隔结构下，封装在内部脂质体中的分子在泄漏到外部环境之前必须渗透通过两个连续的膜，而不是单个膜。通过观察环丙沙星药物的血清半衰期从单一脂质体中的10 min增加到囊泡体中的6 h，证明了这种双膜效应。[7]其他报告证明了这种囊泡体对经皮给药[8]和口服给药[9]的生物医学影响，这是药物输送和癌症治疗的重要领域。一般来说，更复杂或分隔的结构已经开始出现，因为它们能够实现前所未有的控制水平，特别是在药物输送[10]和封闭反应器领域。[11]然而，将多个不同的组分封装在单个隔室中[13]并控制其稳定性和释放特性仍然非常具有挑战性[12]。这种基于聚合物的囊泡体结构可称为“聚合物囊泡中的聚合物囊泡”，最近已有报道。最新的方法之一是通过溶剂置换法（或纳米沉淀法）形成较大的聚合物囊泡，其中较小的聚合物囊泡先前通过膜再水化形成的悬浮液作为水相。[14]这种技术的缺点主要在于纳米沉淀过程中的包封产率差。为了克服这种限制，已经研究了其他选择，例如乳液或双重乳液技术。第一个接受这项挑战的团队使用了两种连续的乳液。[15]即使是非常原始的，这样的过程也不是最容易使用的，并且可能缺乏再现性和同质性。Weitz及其同事使用微流体技术形成了另一种类型的复杂聚合物囊泡，聚合物囊泡的聚集体或多室囊泡。[13]这种方法允许高水平的控制和再现性，最近已进一步扩展到完全多区室化的聚合物囊泡。[16]在这里，我们证明了聚合物囊泡体的产生，即聚合物囊泡中的聚合物囊泡，具有原始的，简便的，多功能的，可重复的，低时间和低产品消耗的技术。我们的方法允许多室封装和具有受控渗透性的系统的形成，因为它们呈现出封装在内部聚合物囊泡中的抗癌药物多柔比星（DOX）的释放速率的显著降低。内部聚合物囊泡是由聚（三亚甲基碳酸酯）-b-聚（L-谷氨酸）（PTMC-b-PGA）按照报道的方法合成的纳米沉淀形成的。[17]然后通过乳液离心[18]以定量加载效率将该悬浮液加载到较大的聚（丁二烯）-b-聚（环氧乙烷）（PB-b-PEO）聚合物囊泡中。形成巨大PB-b-PEO聚合物囊泡的过程受到Li及其同事的启发。[19]简而言之（方案1，第1部分），将一小部分水溶液的反相乳液（在这种情况下是纳米尺寸的聚合物囊泡悬浮液）...
Polymer vesicles polymersomes are vesicles obtained from the self-assembly of amphiphilic block copolymers in aqueous solution as a result of free-energy minimization.[1] Their potential use as drug delivery systems,[2] sensors, and/or nanoreactors [3] has recently attracted a great deal of interest.[4] Polymersomes exhibit larger mechanical stability and lower permeability than liposomes, their structural analogues that often suffer from premature drug leakage.[5] To circumvent this limitation, Zasadzinski and co-workers developed liposomes in liposomes structures, also referred as “vesosomes”.[6] With such a compartmentalized structure, a molecule encapsulated in the inner liposome, would have to permeate through two successive membranes, instead of a single one before leaking into the outside environment. This double-membrane effect was demonstrated by observing the serum half-life of ciprofloxacin drug increasing from 10 min in single liposomes to 6h in vesosomes.[7] Other reports evidenced the biomedical impact of such vesosomes for transcutaneous,[8] and oral administration,[9] important areas in drug delivery and cancer therapy. More complex or compartmentalized structures in general, have started to appear because they enable an unprecedented level of control, in particular in the fields of drug delivery [10] and confined reactors.[11] However, it is still very challenging [12] to encapsulate multiple distinct components in a single compartment [13] and control their stability and release properties. Such vesosome structures based on polymers that can be termed “polymersomes in polymersomes” have recently been reported. One of the most recent approaches consisted in forming the larger polymersomes by solvent-displacement method (or nanoprecipitation) with a suspension of smaller polymersomes previously formed by film rehydration as a water phase.[14] The drawback of this technique lies essentially in the poor encapsulation yield during nanoprecipitation. To overcome this limitation, other options, such as emulsions or double-emulsion techniques, have been investigated. The first team taking up this challenge used two successive emulsions.[15] Even if very original, such a process is not the most easy to use and may suffer from a lack of reproducibility and homogeneity. Weitz and co-workers formed another type of complex polymersomes, aggregates of polymersomes, or multicompartment vesicles using microfluidics.[13] Such an approach allows a high level of control and reproducibility that has recently been extended further to fully multicompartmentalized polymersomes.[16] Herein, we demonstrate the generation of polymer vesosomes, that is, polymersomes in polymersomes, with an original, facile, versatile, reproducible, and low-time and lowproduct-consuming technique. Our method allows multiple compartment encapsulation and the formation of systems that have controlled permeability, as they present a significant decrease in the release rate of the anticancer drug doxorubicin (DOX) encapsulated in the inner polymersomes. The inner polymersomes are formed by nanoprecipitation of poly (trimethylene carbonate)-b-poly (L-glutamic acid)(PTMC-b-PGA) synthesized following a reported method.[17] This suspension is then loaded in larger polymersomes of poly (butadiene)-b-poly (ethylene oxide)(PB-b-PEO) by emulsion–centrifugation [18] with a quantitative loading efficiency. The procedure for forming giant PB-b-PEO polymersomes was inspired from Li and co-workers.[19] Briefly (Scheme 1, Part 1), a small fraction of an inverted emulsion of aqueous solution (in this case a nanosize polymersome suspension of …