Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, Innsbruck, Austria; Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, Innsbruck, Austria.
Eur J Pharm Biopharm. 2018 Aug;129:154-161. doi: 10.1016/j.ejpb.2018.05.032. Epub 2018 May 28.
The aim of the study is the evaluation of the impact of glyceryl ester surfactants on cell permeating properties of SEDDS (self-emulsifying drug delivery systems).
SEDDS containing the glyceryl ester surfactants polyglyceryl-3-stearate (TGlysurf9), polyglyceryl-5-oleate (TGlysurf11.5) and glyceryl stearate citrate (TGlysurf12) were prepared and characterized regarding droplet size and zeta potential. Toxicity studies were performed on Caco-2 cells using resazuring assay. The formulations were loaded with fluorescein diacetate (FDA) and curcumin, and cell uptake studies on Caco-2 cells were performed. Cell uptake was visualized via real time live confocal microscopy. Cell permeability of the SEDDS was tested and trans-epithelial electrical resistance (TEER) measurements were performed. Furthermore, the anti-proliferative and anti-migration activity of curcumin loaded in the SEEDS was investigated.
The developed SEDDS (0.05% m/v) showed no cytotoxicity on Caco-2 cells after 3 h of incubation. Glyceryl esters-SEDDS showed a significant higher FDA and curcumin cell uptake than SEDDS without glyceryl ester surfactants (p < 0.05). TGlysurf9-SEDDS showed thereby the most pronounced permeation enhancing properties. TEER remained constant during the permeation study. Curcumin loaded in TGlysurf9-SEDDS exhibited 1.9-fold higher anti-proliferative effect than curcumin loaded in SEDDS without glyceryl ester surfactants. Furthermore, curcumin loaded in glyceryl ester-SEDDS inhibited Caco-2 cells migration to a higher extent than unloaded curcumin and curcumin loaded in SEDDS without the glyceryl ester surfactants.
Glyceryl ester surfactants and in particular polyglyceryl-3-stearate might be a promising excipient for the formulation of SEDDS exhibiting enhanced cellular uptake and permeation enhancing properties.
本研究旨在评估甘油酯表面活性剂对 SEDDS（自乳化药物传递系统）细胞渗透性能的影响。
制备并表征含有甘油酯表面活性剂聚甘油-3-硬脂酸酯（TGlysurf9）、聚甘油-5-油酸酯（TGlysurf11.5）和甘油硬脂酸柠檬酸酯（TGlysurf12）的 SEDDS，考察其粒径和zeta 电位。采用 Resazurin 测定法对 Caco-2 细胞进行毒性研究。将 FDA 和姜黄素负载到配方中，在 Caco-2 细胞上进行细胞摄取研究。通过实时活细胞共聚焦显微镜观察细胞摄取情况。测试 SEDDS 的细胞通透性并进行跨上皮电阻（TEER）测量。此外，还研究了负载在 SEEDS 中的姜黄素的抗增殖和抗迁移活性。
开发的 SEDDS（0.05%m/v）在孵育 3 小时后对 Caco-2 细胞无细胞毒性。与不含甘油酯表面活性剂的 SEDDS 相比，甘油酯-SEDDS 显示出更高的 FDA 和姜黄素细胞摄取（p<0.05）。TGlysurf9-SEDDS 表现出最显著的渗透增强特性。在渗透研究过程中，TEER 保持不变。负载在 TGlysurf9-SEDDS 中的姜黄素比负载在不含甘油酯表面活性剂的 SEDDS 中的姜黄素表现出 1.9 倍更高的抗增殖作用。此外，负载在甘油酯-SEDDS 中的姜黄素抑制 Caco-2 细胞迁移的程度高于未负载的姜黄素和负载在不含甘油酯表面活性剂的 SEDDS 中的姜黄素。
甘油酯表面活性剂，特别是聚甘油-3-硬脂酸酯，可能是一种有前途的 SEDDS 赋形剂，具有增强的细胞摄取和渗透增强特性。
