Biological & Soft Matter Research Group, Department of Physics, Faculty of Natural, Mathematical & Engineering Sciences, King's College London, London, UK.
Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Stopford Building, Oxford Road, Manchester, UK.
Nanoscale. 2024 Feb 1;16(5):2642-2653. doi: 10.1039/d3nr05083a.
Lipid-based drug carriers are an attractive option to solubilise poorly water soluble therapeutics. Previously, we reported that the digestion of a short tail PC lipid (2C6PC) by the PLA2 enzyme has a significant effect on the structure and stability of the micelles it forms. Here, we studied the interactions of micelles of varying composition representing various degrees of digestion with a model ordered (70 mol% DPPC & 30 mol% cholesterol) and disordered (100% DOPC) lipid membrane. Micelles of all compositions disassociated when interacting with the two different membranes. As the percentage of digestion products (C6FA and C6LYSO) in the micelle increased, the disassociation occurred more rapidly. The C6FA inserts preferentially into both membranes. We find that all micelle components increase the area per lipid, increase the disorder and decrease the thickness of the membranes, and the 2C6PC lipid molecules have the most significant impact. Additionally, there is an increase in permeation of water into the membrane that accompanies the insertion of C6FA into the DOPC membranes. We show that the natural digestion of lipid micelles result in molecular species that can enhance the permeability of lipid membranes that in turn result in an enhanced delivery of drugs.
基于脂质的药物载体是增溶疏水性治疗药物的一种有吸引力的选择。此前，我们报道过短尾 PC 脂质（2C6PC）被 PLA2 酶消化后，对其形成的胶束的结构和稳定性有显著影响。在这里，我们研究了具有不同组成的胶束与模型有序（70mol% DPPC 和 30mol%胆固醇）和无序（100%DOPC）脂质膜之间的相互作用。与两种不同的膜相互作用时，所有组成的胶束都解离了。随着胶束中消化产物（C6FA 和 C6LYSO）的百分比增加，解离发生得更快。C6FA 优先插入两种膜中。我们发现所有胶束成分都增加了每个脂质的面积，增加了无序性并减小了膜的厚度，其中 2C6PC 脂质分子的影响最大。此外，伴随着 C6FA 插入 DOPC 膜，水向膜内的渗透也会增加。我们表明，脂质胶束的天然消化会产生可以增强脂质膜通透性的分子种类，从而增强药物的递送。
