Langmuir. 2024 Nov 5;40(44):23521-23528. doi: 10.1021/acs.langmuir.4c03322. Epub 2024 Oct 23.
Liposomal drug delivery is a promising approach for delivering therapeutics effectively. While most liposomes are designed to be nanometer-sized for efficient cellular uptake, micron-sized liposomes are gaining interest due to their larger drug-loading capacity. When combined with macroscale structures, such as implants and hydrogels, they offer prolonged therapeutic delivery. This study investigates how solvents affect the production of micron-sized liposomes, with or without cholesterol, using the reverse-phase evaporation (RPE) method. Although the RPE method is established for producing micron-sized liposomes, the influence of solvents on liposome size and uniformity is not well understood. The study explores whether controlling the size of inverse micelles, an intermediate product, through the use of different organic solvents affects the final liposome size. Three solvents─diethyl ether, methanol, and acetone─were tested for their effect on the formation of inverse micelles and liposomes and their sizes. Results showed that without cholesterol, diethyl ether produced uniform inverse micelles, leading to mostly nanosized liposomes. Methanol and acetone resulted in phase separation, preventing uniform liposome formation, although some micron-sized liposomes appeared. The acetone sample yielded mostly oil droplets. The results showed that forming inverse micelles lead to nanosized liposomes. With cholesterol, phase separation was dominant in methanol, but micron-sized liposomes still formed. Across all cases, cholesterol reduced the liposome size. The findings reveal that inverse micelles are not always reliable predictors of the final liposome size and that the RPE method is highly sensitive to solvent polarity and lipid-solvent interactions. Overall, the findings of this study provide valuable insights into how the choice of solvent and lipid composition can influence the production of liposomes via the RPE method. These insights are critical for optimizing liposome production and influencing future designs of liposomal drug delivery systems.
脂质体药物递送是一种有前途的有效递药方法。虽然大多数脂质体被设计为纳米级以实现高效细胞摄取，但微米级脂质体由于其更大的载药能力而受到关注。当与宏观结构（如植入物和水凝胶）结合时，它们提供了延长的治疗性递药。本研究探讨了溶剂如何影响使用反相蒸发（RPE）方法制备载药或未载药的微米级脂质体。尽管 RPE 方法已被确立用于制备微米级脂质体，但溶剂对脂质体大小和均匀性的影响尚未得到很好的理解。本研究探索了通过使用不同有机溶剂控制中间产物反胶束的大小是否会影响最终脂质体的大小。研究了三种溶剂——二乙醚、甲醇和丙酮——对反胶束形成和脂质体及其大小的影响。结果表明，在没有胆固醇的情况下，二乙醚产生均匀的反胶束，导致主要形成纳米级脂质体。甲醇和丙酮导致相分离，阻止了均匀的脂质体形成，尽管出现了一些微米级脂质体。丙酮样品主要生成油滴。结果表明，形成反胶束会导致纳米级脂质体的形成。加入胆固醇后，甲醇中主要发生相分离，但仍形成微米级脂质体。在所有情况下，胆固醇都减小了脂质体的大小。研究结果表明，反胶束并不总是最终脂质体大小的可靠预测指标，并且 RPE 方法对溶剂极性和脂质-溶剂相互作用非常敏感。总的来说，本研究的结果提供了有关溶剂和脂质组成如何通过 RPE 方法影响脂质体生产的有价值的见解。这些见解对于优化脂质体生产和影响未来的脂质体药物递送系统设计至关重要。
