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用于原位形成纯化脂质体的透析功能化微流控平台。

Dialysis-functionalized microfluidic platform for in situ formation of purified liposomes.

机构信息

Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha 410008, China; State Key Laboratory of Precision Manufacturing for Extreme Service Performance, College of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China.

State Key Laboratory of Precision Manufacturing for Extreme Service Performance, College of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China.

出版信息

Colloids Surf B Biointerfaces. 2024 Apr;236:113829. doi: 10.1016/j.colsurfb.2024.113829. Epub 2024 Feb 28.

DOI:10.1016/j.colsurfb.2024.113829
PMID:38430829
Abstract

Continuous-flow microfluidic devices have been extensively used for producing liposomes due to their high controllability and efficient synthesis processes. However, traditional methods for liposome purification, such as dialysis, gel chromatography, and ultrafiltration, are incompatible with microfluidic devices, which would dramatically restrict the efficiency of liposome synthesis. In this study, we developed a dialysis-functionalized microfluidic platform (DFMP) for in situ formation of purified drug-loaded liposomes. The device was successfully fabricated by using a high-resolution projection micro stereolithography (PμSL) 3D printer. The integrated DFMP consists of a microfluidic mixing unit, a microfluidic dialysis unit, and a dialysis membrane, enabling the liposome preparation and purification in one device. The purified ICG-loaded liposomes prepared by DFMP had a smaller size (264.01±5.34 nm to 173.93±10.71 nm) and a higher encapsulation efficiency (EE) (43.53±0.07% to 46.07±0.67%). In vivo photoacoustic (PA) imaging experiment demonstrated that ICG-loaded liposomes purified with microfluidic dialysis exhibited a stronger penetration and accumulation (2-3 folds) in tumor sites. This work provides a new strategy for one-step production of purified drug-loaded liposomes.

摘要

连续流微流控装置由于其高可控性和高效的合成工艺,已被广泛用于制备脂质体。然而,脂质体的传统纯化方法,如透析、凝胶层析和超滤等,与微流控装置不兼容,这将极大地限制脂质体的合成效率。在本研究中,我们开发了一种用于原位形成纯化载药脂质体的透析功能化微流控平台(DFMP)。该装置是通过使用高分辨率投影微立体光刻(PμSL)3D 打印机成功制造的。集成的 DFMP 由微流混合单元、微流透析单元和透析膜组成,可在一个装置中完成脂质体制备和纯化。DFMP 制备的纯化 ICG 载药脂质体具有更小的粒径(264.01±5.34nm 至 173.93±10.71nm)和更高的包封效率(EE)(43.53±0.07%至 46.07±0.67%)。体内光声(PA)成像实验表明,用微流透析纯化的 ICG 载药脂质体在肿瘤部位具有更强的穿透和积累能力(2-3 倍)。这项工作为一步法制备纯化载药脂质体提供了一种新策略。

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