Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Int J Pharm. 2022 Aug 25;624:122014. doi: 10.1016/j.ijpharm.2022.122014. Epub 2022 Jul 16.
In this study PEG-free and zeta potential changing lipid-based nanocarriers providing enhanced cellular uptake were developed. Nanostructured lipid carriers (NLC), consisting of paraffin wax, caprylic/ capric triglyceride, cetyltrimethylammoniumchloride and either soy lecithin or polyglycerol-4 laurate and solid lipid nanoparticles (SLN) with the same composition but without the liquid lipid content were developed. All formulations exposed a positive surface charge and were then coated with the polyphosphate Graham's salt. Phosphate release from these formulations was evaluated by incubation with intestinal alkaline phosphatase as well as on a Caco-2 monolayer and zeta potentials were measured. Additionally, cellular uptake studies were performed. Within 5 h, a remarkable amount of phosphate was released from all formulations incubated with intestinal alkaline phosphatase. Enzymatically induced phosphate release with intestinal alkaline phosphatase led to a zeta potential shift up to Δ 26 mV. Results of phosphate release and zeta potential change were confirmed on Caco-2 cells. Cellular uptake studies on Caco-2 cells showed an up to 5.6-times higher uptake compared to cells with inhibited phosphatase. According to these results, polyphosphate coating is a powerful tool to obtain lipid-based nanocarriers for enhanced cellular uptake.
在这项研究中，开发了无聚乙二醇（PEG）和具有正表面电荷且能够改变 ζ 电位的基于脂质的纳米载体，以提高细胞摄取率。纳米结构脂质载体（NLC）由石蜡、辛酸/癸酸三甘油酯、十六烷基三甲基氯化铵和大豆卵磷脂或聚甘油-4 月桂酸酯组成，而固体脂质纳米粒（SLN）则具有相同的组成但不含液态脂质。所有制剂均具有正表面电荷，然后用聚磷酸盐 Graham 盐进行包衣。通过与肠碱性磷酸酶孵育以及在 Caco-2 单层上评估这些制剂的磷酸盐释放，并测量 ζ 电位。此外，还进行了细胞摄取研究。在 5 小时内，与肠碱性磷酸酶孵育的所有制剂均释放出大量的磷酸盐。用肠碱性磷酸酶诱导的磷酸盐释放导致 ζ 电位上升高达 26 mV。在 Caco-2 细胞上证实了磷酸盐释放和 ζ 电位变化的结果。在 Caco-2 细胞上进行的细胞摄取研究表明，与抑制磷酸酶的细胞相比，摄取率提高了 5.6 倍。根据这些结果，多磷酸盐包衣是获得用于增强细胞摄取的基于脂质的纳米载体的有力工具。
