Unveiling the impact of membrane fluidity in shaping lipid-based drug delivery systems development

Membrane fluidity is a fundamental property extensively studied in biological membranes and biophysical research, where it is critical to understanding membrane structure and function. However, its application in the development and manufacturing of lipid-based drug delivery systems, such as liposomes and lipid nanoparticles, remains underexplored. This mini-review shifts the focus toward the practical implications of membrane fluidity in pharmaceutical formulation and manufacturing. We highlight key factors influencing fluidity, such as temperature, lipid composition, and cholesterol content, and emphasize how understanding and controlling fluidity can serve as a critical quality attribute. The importance of these factors in modulating membrane dynamics is emphasized, revealing their potential to optimize liposomal formulations and manufacturing processes. Fluorescent probes such as DPH and Laurdan are also discussed for their ability to monitor fluidity in real-time, each presenting distinct advantages and limitations. Although its crucial role in lipid-based drug delivery systems, membrane fluidity remains a largely overlooked property. Deeper investigation is essential to fully understand its influence on membrane stability, therapeutic efficacy, and scalability. This mini-review advocates for a paradigm shift: recognizing membrane fluidity as a critical quality attribute that can be integrated into formulation development and industrial manufacturing frameworks to better predict and control product performance and process robustness.