Department of Physics, University of Zanjan, 45195-313 Zanjan, Iran.
Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 45137-66731, Iran.
Int J Pharm. 2019 Mar 25;559:173-181. doi: 10.1016/j.ijpharm.2019.01.036. Epub 2019 Jan 23.
Lipid-based drug delivery systems are considered as promising vehicles for hydrophobic drug compounds. Lipid distribution within the droplet can affect drug loading capacity in these carriers. However, it is extremely challenging to determine the nanostructure within these carriers through the implementation of the direct experimental methods due to the ultrafine size. Therefore, coarse grained molecular dynamics (MD) simulation was utilized to model different kinds of lipid-based nanoparticles of the diameter about 12 nm including solid lipid nanoparticles (SLN), nanoemulsion (NE), and nanostructured lipid carriers (NLC), and the organization of the lipids within the carriers was explored. The aforementioned nanoparticles consisted of stearic acid, oleic acid as lipids, and sodium dodecyl sulfate (SDS) as a surfactant in water medium. Furthermore, the impact of solid to liquid mass ratio on the lipid distribution within the lipid matrix was investigated regarding the NLC simulations. In the equilibrium state, we observed the vesicle-like structure for all the investigated systems in which the hydrophilic moieties of the lipids and surfactant organized a semi-bilayer fold into the droplet and the hydrophobic tails accumulated among them. It is worth mentioning although SDS as a harsh surfactant, which is a special case, was expected to be present in the surface of the droplet, it penetrated into the lipids. Additionally, our results showed remarkable entrapped water beads inside the droplet in the form of one or more cavities along the internal layer of the head groups which was surrounded by lipid head groups. It was also reported that in the building structure of the nanoemulsion and SLN, in the central parts of the droplets, lipids were denser than the case of NLCs. Moreover, no crystallization occurred within the lipid-based carriers. Finally, the results indicated that, in the case of NLC simulations, the lipid distribution within the lipid matrix was insensitive to the mass fraction of solid to liquid lipids.
基于脂质的药物传递系统被认为是疏水药物化合物的有前途的载体。脂质在液滴中的分布会影响这些载体中的药物载药量。然而，由于这些载体的超细微尺寸，通过直接实验方法来确定其纳米结构极具挑战性。因此，利用粗粒分子动力学（MD）模拟来模拟不同种类的直径约为 12nm 的基于脂质的纳米颗粒，包括固体脂质纳米颗粒（SLN）、纳米乳（NE）和纳米结构脂质载体（NLC），并探索了载体中脂质的组织。上述纳米颗粒由硬脂酸、油酸作为脂质，以及十二烷基硫酸钠（SDS）作为水介质中的表面活性剂组成。此外，还针对 NLC 模拟研究了固液质量比对脂质在脂质基质内分布的影响。在平衡状态下，我们观察到所有被研究系统都呈现出类似囊泡的结构，其中脂质和亲水表面活性剂的亲水部分在液滴中组织成半双层折叠，疏水性尾部在它们之间聚集。值得一提的是，尽管 SDS 是一种苛刻的表面活性剂，是一个特殊情况，预计会存在于液滴的表面，但它也渗透到了脂质中。此外，我们的结果表明，在液滴内部以一个或多个空腔的形式存在着大量的被包裹水珠，这些空腔沿着头部基团的内层排列，被头部基团的脂质所包围。还报道称，在纳米乳和 SLN 的构建结构中，在液滴的中心部分，脂质的密度比 NLC 中的更高。此外，在基于脂质的载体中没有发生结晶。最后，结果表明，在 NLC 模拟中，脂质在脂质基质内的分布对固液脂质的质量分数不敏感。
