ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville, Victoria 3052, Australia; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville, Victoria 3052, Australia.
J Colloid Interface Sci. 2019 Nov 1;555:361-372. doi: 10.1016/j.jcis.2019.07.081. Epub 2019 Jul 28.
Drug nanocrystals precipitated inside liposomes are of increasing interest in liposomal drug delivery. For liposomal nanocrystal formulations, the size and shape of the drug nanocrystals can influence the apparent drug release properties, providing opportunities for developing tailored liposomal drug release systems. Small angle X-ray scattering (SAXS) and quantitative transmission electron microscopy (TEM) can be used to analyse the size distributions of the nanoparticles. In this study, by changing the fluidity of the membrane through the use of different membrane phospholipids with varying cholesterol content, the impact of lipid phase, fluidity and permeability on the size distribution of ciprofloxacin nanocrystals were investigated using standard TEM and SAXS as orthogonal techniques. The results show that the phospholipid phase behaviour has a direct effect on the nanocrystal size distribution, where shorter and thinner nanocrystals were formed in liposomes made from hydrogenated soy phosphatidylcholine (HSPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) phospholipids with higher phase transition temperatures than 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) with lower transition temperatures. This is mainly due to the phase behaviour of the liposome during nanocrystal formation. The addition of cholesterol that reduces fluidity and permeability of the DOPC liposomes was also shown to restrict the growth of the ciprofloxacin nanocrystals. Moreover, increasing the drug loading of the liposomes made from HSPC and DPPC produced longer and wider nanocrystals. The findings open new opportunities to tailor nanocrystal size distributions, as well as the aspect ratio of the enclosing liposomes with potential to alter drug release and in vivo behaviour.
脂质体内部沉淀的药物纳米晶体在脂质体药物传递中越来越受到关注。对于脂质体纳米晶体制剂，药物纳米晶体的大小和形状可以影响药物的表观释放特性，为开发定制的脂质体药物释放系统提供了机会。小角 X 射线散射（SAXS）和定量透射电子显微镜（TEM）可用于分析纳米颗粒的粒径分布。在这项研究中，通过使用不同胆固醇含量的膜磷脂来改变膜的流动性，使用标准 TEM 和 SAXS 作为正交技术，研究了脂质相、流动性和通透性对环丙沙星纳米晶体粒径分布的影响。结果表明，磷脂相行为对纳米晶体粒径分布有直接影响，其中在具有较高相变温度的氢化大豆磷脂酰胆碱（HSPC）和 1,2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC）磷脂制成的脂质体中形成了更短更细的纳米晶体，而相变温度较低的 1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱（DMPC）和 1,2-二油酰基-sn-甘油-3-磷酸胆碱（DOPC）则形成了更短更细的纳米晶体。这主要是由于在纳米晶体形成过程中脂质体的相行为。此外，添加胆固醇降低了 DOPC 脂质体的流动性和通透性，也限制了环丙沙星纳米晶体的生长。此外，增加 HSPC 和 DPPC 制成的脂质体的载药量会产生更长更宽的纳米晶体。这些发现为定制纳米晶体粒径分布以及改变药物释放和体内行为的包封脂质体的纵横比提供了新的机会。
