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使用膜接触器制备脂质体和非离子囊泡用于放大。

Liposome and niosome preparation using a membrane contactor for scale-up.

机构信息

Université de Lyon, F-69622 Lyon, France.

出版信息

Colloids Surf B Biointerfaces. 2012 Jun 1;94:15-21. doi: 10.1016/j.colsurfb.2011.12.036. Epub 2012 Jan 21.

Abstract

The scaling-up ability of liposome and niosome production, from laboratory scale using a syringe-pump device to a pilot scale using the membrane contactor module, was investigated. For this aim, an ethanol injection-based method was applied for liposome and niosome preparation. The syringe-pump device was used for laboratory scale batches production (30 ml for liposomes, 20 ml for niosomes) then a pilot scale (750 ml for liposomes, 1000 ml for niosomes) were obtained using the SPG membrane contactor. Resulted nanovesicles were characterized in terms of mean vesicles size, polydispersity index (PdI) and zeta potential. The drug encapsulation efficiency (E.E.%) was evaluated using two drug-models: caffeine and spironolactone, a hydrophilic and a lipophilic molecule, respectively. As results, nanovectors mean size using the syringe-pump device was comprised between 82 nm and 95 nm for liposomes and between 83 nm and 127 nm for niosomes. The optimal E.E. of caffeine within niosomes, was found around 9.7% whereas the spironolactone E.E. reached 95.6% which may be attributed to its lipophilic properties. For liposomes these values were about 9.7% and 86.4%, respectively. It can be clearly seen that the spironolactone E.E. was slightly higher within niosomes than liposomes. Optimized formulations, which offered smaller size and higher E.E., were selected for pilot scale production using the SPG membrane. It has been found that vesicles characteristics (size and E.E.%) were reproducible using the membrane contactor module. Thus, the current study demonstrated the usefulness of the membrane contactor as a device for scaling-up both liposome and niosome preparations with small mean sizes.

摘要

考察了从使用注射器泵装置的实验室规模到使用膜接触器模块的中试规模扩大脂质体和非离子囊泡生产的能力。为此,应用基于乙醇注入的方法制备脂质体和非离子囊泡。使用注射器泵装置进行实验室规模批次生产(脂质体 30ml,非离子囊泡 20ml),然后使用 SPG 膜接触器获得中试规模(脂质体 750ml,非离子囊泡 1000ml)。从平均囊泡尺寸、多分散指数(PdI)和zeta 电位方面对所得纳米囊泡进行了表征。使用两种药物模型(咖啡因和螺内酯)评估药物包封效率(E.E.%),它们分别是亲水性和疏水性分子。结果,使用注射器泵装置的纳米载体平均粒径在 82nm 到 95nm 之间,用于脂质体;在 83nm 到 127nm 之间,用于非离子囊泡。非离子囊泡中咖啡因的最佳 E.E.约为 9.7%,而螺内酯的 E.E.达到 95.6%,这可能归因于其疏水性。对于脂质体,这些值分别约为 9.7%和 86.4%。可以清楚地看到,非离子囊泡中的螺内酯 E.E.略高于脂质体。使用 SPG 膜对优化后的制剂进行中试规模生产,选择粒径较小和 E.E.较高的制剂。研究发现,使用膜接触器模块可以重现囊泡的特征(粒径和 E.E.%)。因此,本研究表明膜接触器是一种有用的设备,可用于从小规模扩大脂质体和非离子囊泡的制备。

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