紫杉醇负载的pH敏感脂质体：结构和物理化学表征的新见解,Langmuir

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紫杉醇负载的pH敏感脂质体：结构和物理化学表征的新见解
Langmuir ( IF 3.7 ) Pub Date : 2018-04-20 00:00:00 , DOI: 10.1021/acs.langmuir.8b00411
Liziane O. F. Monteiro , Ângelo Malachias , Gwenaelle Pound-Lana ₁ , Rogério Magalhães-Paniago , Vanessa C. F. Mosqueira ₁ , Mônica C. Oliveira , André Luís B. de Barros , Elaine A. Leite

Affiliation

我们小组最近开发了一种含有紫杉醇的长循环且对pH敏感的脂质体（SpHL-PTX）。一旦处于酸性环境（例如肿瘤）中，这些脂质体就会不稳定，从而释放出包封的药物。这样，本研究的目的是评估在相似的生物环境条件下，脂质双层和PTX之间的分子和超分子相互作用。SpHL-PTX结构的高灵敏度分析是通过小角度X射线散射技术与其他技术（例如动态光散射，不对称流场流分馏，透射电子显微镜和高效液相色谱法）相结合而获得的。结果表明，PTX掺入脂质体双层中会明显导致油酰磷脂酰乙醇胺（DOPE）分子的超分子组织发生变化，从而诱导形成更有序的结构。在较低的pH下观察到超分子组织的变化，表明即使在胎牛血清蛋白存在的情况下，pH敏感性也得以保留。此外，SpHL-PTX的形态和理化特性证明了适合静脉内给药的纳米级分散体的形成。总之，在pH 7.4时可获得稳定的纳米级PTX分散体，并具有适合静脉内给药的参数。在较低的pH条件下，DOPE分子的超分子组织的变化清楚地证明了系统的pH敏感性，这对于将PTX传递到目标细胞的细胞质中至关重要。这样，通过不同技术获得的结果证实了SpHL作为在酸性环境（例如肿瘤）中PTX递送的有前途工具的可行性。

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Paclitaxel-Loaded pH-Sensitive Liposome: New Insights on Structural and Physicochemical Characterization

A long-circulating and pH-sensitive liposome containing paclitaxel (SpHL-PTX) was recently developed by our group. Once in an acidic environment, for example, tumors, these liposomes undergo destabilization, releasing the encapsulated drug. In this way, the aim of this study was to evaluate the molecular and supramolecular interactions between the lipid bilayer and PTX in similar biological environment conditions. High-sensitivity analyses of SpHL-PTX structures were obtained by the small-angle X-ray scattering technique combined with other techniques such as dynamic light scattering, asymmetric flow field-flow fractionation, transmission electron microscopy, and high-performance liquid chromatography. The results showed that PTX incorporation in the liposomal bilayer clearly leads to changes in supramolecular organization of dioleoylphosphatidylethanolamine (DOPE) molecules, inducing the formation of more ordered structures. Changes in supramolecular organization were observed at lower pH, indicating that pH sensitivity was preserved even in the presence of fetal bovine serum proteins. Furthermore, morphological and physicochemical characterization of SpHL-PTX evidenced the formation of nanosized dispersion suitable for intravenous administration. In conclusion, a stable nanosized dispersion of PTX was obtained at pH 7.4 with suitable parameters for intravenous administration. At lower pH conditions, the pH sensitivity of the system was clearly evidenced by changes in the supramolecular organization of DOPE molecules, which is crucial for the delivery of PTX into the cytoplasm of the targeted cells. In this way, the results obtained by different techniques confirm the feasibility of SpHL as a promising tool to PTX delivery in acidic environments, such as tumors.

更新日期：2018-04-20

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