Start Publications High throughput onion-like liposome formation with efficient ...
QSense

High throughput onion-like liposome formation with efficient protein encapsulation under flash antisolvent mixing

Year: 2022

Journal: J. Colloid Interface Sci., Volume 618, JUL 15, page 185–195

Authors: Zhan, Qiang-Wei; Gao, Jun; Li, Dongcui; Huang, Yan

Organizations: National Natural Science Foun-dation of China [31801492]; Natural Science Founda-tion of Fujian Province [2019 J01641]

Keywords: Liposome; Bovine Serum Albumin; Quartz Crystal Microbalance with; Dissipation; Flash Nano-Precipitation

Achieving a high encapsulation efficiency and loading capacity of proteins in lecithin-based liposomes has always been a challenge. Here, we use Flash Nano-Precipitation (FNP) to produce liposomes and investigated the encapsulation of model protein (Bovine Serum Albumin, BSA). Through rapid turbulent mixing, we obtained liposomes with small size, low polydispersity, and good batch repeatability at a high production rate. We demonstrated that the bilayer of liposomes prepared solely using lecithin was defective, which led to the fusion, and increased size and polydispersity. When cholesterol was added to reach a lecithin-to-cholesterol molar ratio of 5:3, a compact bilayer formed to effectively inhibit liposome fusion. The encapsulation efficiency and loading capacity of BSA was as high as ti 68% and - 6% in lecithin-cholesterol liposome, respectively, far exceeding the values reported in the literature. Further study by Quartz Crystal Microbalance with Dissipation (QCM-D) revealed that the highly effective encapsulation was due to the rapid mutual adsorption between BSA and defective/curved lecithin double layers during the liposome formation. Such rapid mutual adsorption leads to the layer-by-layer assembly and formation of onion-like compact liposome structure as revealed by Cryo-TEM. This simple FNP method provides a scalable manufacturing approach for liposomes with efficient protein encapsulation. The revealed adsorption mechanism between protein and lecithin bilayers could also serve as a guide for similar studies.