AC electrokinetic mixing-assisted controllable liposome synthesis using a mold-extraction fabricated microfluidic...

Liposomes, as one of the most promising and rapidly evolving drug delivery systems, are highly valued for their biocompatibility, ability to encapsulate diverse drugs, controlled release, and targeted delivery, offering enhanced therapeutic effects with reduced toxicity. However traditional methods for synthesizing liposomes still exhibit problems such as uncontrollable particle size and uneven distribution, reducing passive targeting efficiency and compromising treatments In present study, we introduce a novel alternating current electrokinetic mixing-assisted micro-synthesis method for liposome production, utilizing a novel custom (mold-extraction) approach to fabricate a 3D-structured microfluidic chip with parallel electrodes along both sides of the channel. Unlike traditional methods, where etched thin electrodes often result in non-uniform electric fields and leakage, the present method enables the placement of 3D electrodes with channel thickness, minimizes electrode distance, and allows for the generation of a strong, uniform electric field at low voltages. Consequently, controllable ultra-fast active mixing is achieved, resulting in the controlled and adjustable synthesis of liposomes with uniform size distributions. The effects of flow rate,E(electric field intensity), and frequency on the synthesis of liposomes were investigated. Additionally, studies demonstrated that drug encapsulation efficiency can be precisely controlled by modulating the applied electric field, a capability that was further validated through cellular experiments. This study presents a straightforward and adjustable approach for the precise synthesis of liposomes, which can be utilized to develop customized drug delivery systems.