School of Science, College of Science, Engineering and Health, RMIT University , Melbourne, Victoria 3000, Australia.
CSIRO Manufacturing , Clayton, Victoria 3168, Australia.
Langmuir. 2017 Mar 14;33(10):2571-2580. doi: 10.1021/acs.langmuir.6b04045. Epub 2017 Feb 27.
We report here the lyotropic liquid crystalline phase behavior of two lipid nanoparticulate systems containing mixtures of monoolein, capric acid, and saturated diacyl phosphatidylcholines dispersed by the Pluronic F127 block copolymer. Synchrotron small-angle X-ray scattering (SAXS) was used to screen the phase behavior of a library of lipid nanoparticles in a high-throughput manner. It was found that adding capric acid and phosphatidylcholines had opposing effects on the spontaneous membrane curvature of the monoolein lipid layer and hence the internal mesophase of the final nanoparticles. By varying the relative concentration of the three lipid components, we were able to establish a library of nanoparticles with a wide range of mesophases including at least the inverse bicontinuous primitive and double diamond cubic phases, the inverse hexagonal phase, the fluid lamellar phase, and possibly other phases. Furthermore, the in vitro cytotoxicity assay showed that the endogenous phospholipid-containing nanoparticles were less toxic to cultured cell lines compared to monoolein-based counterparts, improving the potential of the nonlamellar lipid nanoparticles for biomedical applications.
我们在此报告了两种包含单油酸甘油酯、癸酸和饱和二酰基磷脂酰胆碱混合物的脂质纳米颗粒系统的溶致液晶相行为，这些系统由 Pluronic F127 嵌段共聚物分散。同步加速器小角 X 射线散射 (SAXS) 被用于高通量筛选脂质纳米颗粒的相行为文库。研究发现，添加癸酸和磷脂酰胆碱对单油酸甘油酯脂质层的自发膜曲率以及最终纳米颗粒的内部中间相具有相反的影响。通过改变三种脂质成分的相对浓度，我们能够建立一个具有广泛中间相的纳米颗粒文库，其中至少包括反向双连续原始相和双立方相、反向六方相、流体层状相，以及可能的其他相。此外，体外细胞毒性试验表明，与基于单油酸甘油酯的纳米颗粒相比，内源性含磷脂的纳米颗粒对培养的细胞系的毒性较小，提高了非层状脂质纳米颗粒在生物医学应用中的潜力。
