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周期性扰动混合器中不同有机溶剂对脂质体性质的影响:潜在的有机溶剂替代品二乙二醇单乙醚

The effect of different organic solvents in liposome properties produced in a periodic disturbance mixer: Transcutol®, a potential organic solvent replacement.

作者信息

López Rubén R, G Font de Rubinat Paula, Sánchez Luz-María, Tsering Thupten, Alazzam Anas, Bergeron Karl-F, Mounier Catherine, Burnier Julia V, Stiharu Ion, Nerguizian Vahé

机构信息

Department of Electrical Engineering, École de technologie supérieure, 1100 Notre Dame-West, Montreal, QC H3C 1K3, Canada.

Department of Electrical Engineering, École de technologie supérieure, 1100 Notre Dame-West, Montreal, QC H3C 1K3, Canada; Department of Electrical Engineering, ETS d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, 647 Avinguda Diagonal, Barcelona, Catalunya 08028, Spain.

出版信息

Colloids Surf B Biointerfaces. 2021 Feb;198:111447. doi: 10.1016/j.colsurfb.2020.111447. Epub 2020 Nov 4.

DOI:10.1016/j.colsurfb.2020.111447
PMID:33223347
Abstract

Liposomes are versatile particles used in the biomedical field as drug delivery systems (DDS). Liposome production using micromixers have shown to yield nanoparticles for DDS in a single step with a controllable size by changing flow conditions. Nonetheless, other factors such as the organic solvent, play a crucial role in the liposome formation process. Furthermore, drug solubility and toxicity are pivotal when deciding which organic solvent to choose. In this work, liposomes were produced in a periodic disturbance mixer (PDM). We investigated three conventional organic solvents: ethanol, methanol, and isopropanol as well as Transcutol®. We assessed the organic solvent influence on liposome characteristics (size, size distribution and zeta potential). Among the four organic solvents, Transcutol® yielded the smallest liposomes, which ranged from 80 nm to 160 nm. Moreover, a more in-depth investigation showed that Transcutol® produced smaller or similar-sized particles under different temperature and lipid concentration conditions, compared with ethanol. Furthermore, we proved that particles zeta potential was not influenced by the organic solvent, production temperature, or lipid concentration. This work results show that Transcutol® could replace the conventional alcohol-based solvents and can potentially avoid filtration steps due to its low toxicity. Therefore, the present approach is appealing for DDS development.

摘要

脂质体是生物医学领域中用作药物递送系统(DDS)的多功能颗粒。使用微混合器生产脂质体已显示,通过改变流动条件,可在一步中生产出用于DDS的纳米颗粒,且颗粒大小可控。尽管如此,其他因素,如有机溶剂,在脂质体形成过程中起着关键作用。此外,在决定选择哪种有机溶剂时,药物溶解度和毒性至关重要。在这项工作中,脂质体是在周期性扰动混合器(PDM)中生产的。我们研究了三种传统有机溶剂:乙醇、甲醇和异丙醇以及透皮促进剂(Transcutol®)。我们评估了有机溶剂对脂质体特性(大小、大小分布和zeta电位)的影响。在这四种有机溶剂中,透皮促进剂(Transcutol®)产生的脂质体最小,范围在80纳米至160纳米之间。此外,更深入的研究表明,与乙醇相比,在不同温度和脂质浓度条件下,透皮促进剂(Transcutol®)产生的颗粒更小或大小相似。此外,我们证明颗粒的zeta电位不受有机溶剂、生产温度或脂质浓度的影响。这项工作的结果表明,透皮促进剂(Transcutol®)可以替代传统的醇基溶剂,并且由于其低毒性,有可能避免过滤步骤。因此,本方法对药物递送系统(DDS)的开发具有吸引力。

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