Department of Biochemical and Pharmaceutical Technology, University of São Paulo, Av. Prof. Lineu Prestes n 580 Bloco 16, São Paulo, SP, 05508-000, Brazil.
Institute of Physics, University of São Paulo, Rua do Matão, 1371, São Paulo, 05508-090, Brazil.
Drug Deliv Transl Res. 2020 Dec;10(6):1571-1583. doi: 10.1007/s13346-020-00828-y.
Cubosomes are nanoparticles composed of a specific combination of some types of amphiphilic molecules like lipids, such as phytantriol (PHY), and a nonionic polymer, like poloxamer (F127). Cubosomes have a high hydrophobic volume (> 50%) and are good candidates for drug delivery systems. Due to their unique structure, these nanoparticles possess the ability to incorporate highly hydrophobic drugs. A challenge for the encapsulation of hydrophobic molecules is the use of organic solvents in the sample preparation process. In this study, we investigated the structural influence of four different solvents (acetone, ethanol, chloroform, and octane), by means of small-angle X-ray scattering and cryogenic electron microscopy techniques. In the presence of a high amount of acetone and ethanol (1:5 solvent:PHY volumetric ratio), for instance, a cubic-to-micellar phase transition was observed due to the high presence of these two solvents. Chloroform and octane have different effects over PHY-based cubosomes as compared to acetone and ethanol, both of them induced a cubic-to-inverse hexagonal phase transition. Those effects are attributed to the insertion of the solvent in the hydrophobic region of the cubosomes, increasing its volume and inducing such transition. Moreover, a second phase transition from reversed hexagonal-to-inverted micellar was observed for chloroform and octane. The data also suggest that after 24 h of solvent/cubosome incubation, some structural features of cubosomes change as compared to the freshly prepared samples. This study could shed light on drug delivery systems using PHY-based cubosomes to choose the appropriate solvent in order to load the drug into the cubosome.Graphical abstract.
立方纳米载体由特定组合的一些类型的两亲分子组成，如脂质，如植烷三醇（PHY）和非离子聚合物，如泊洛沙姆（F127）。立方纳米载体具有高疏水性体积（>50%），是药物传递系统的良好候选物。由于其独特的结构，这些纳米颗粒具有包含高度疏水性药物的能力。封装疏水分子的一个挑战是在样品制备过程中使用有机溶剂。在这项研究中，我们通过小角 X 射线散射和低温电子显微镜技术研究了四种不同溶剂（丙酮、乙醇、氯仿和辛烷）的结构影响。例如，在存在大量丙酮和乙醇（溶剂：PHY 体积比为 1:5）的情况下，由于这两种溶剂的高存在，观察到立方相向胶束相的转变。与丙酮和乙醇相比，氯仿和辛烷对基于 PHY 的立方纳米载体有不同的影响，它们都诱导立方相向反六方相的转变。这些影响归因于溶剂插入立方纳米载体的疏水区，增加其体积并诱导这种转变。此外，对于氯仿和辛烷，还观察到从反六方相向反转胶束的第二相转变。数据还表明，与新鲜制备的样品相比，在溶剂/立方纳米载体孵育 24 小时后，立方纳米载体的一些结构特征发生了变化。这项研究可以为使用基于 PHY 的立方纳米载体的药物传递系统提供启示，以选择合适的溶剂将药物载入立方纳米载体中。
