利用果胶和壳聚糖修饰的固体脂质纳米颗粒增强牛乳铁蛋白的细胞摄取和转运。
Enhanced Cellular Uptake and Transport of Bovine Lactoferrin Using Pectin- and Chitosan-Modified Solid Lipid Nanoparticles.
发表日期:2023 Aug 21
作者:
Xudong Yao, Craig Bunt, Mengyang Liu, Siew-Young Quek, John Shaw, Jillian Cornish, Jingyuan Wen
来源:
Pharmaceutics
摘要:
该项目旨在利用果胶和壳聚糖修饰的固体脂质纳米颗粒来增强牛乳铁蛋白的细胞摄取和输运。通过溶剂挥发技术,制备了含有牛乳铁蛋白(bLf)的固体脂质颗粒,其中包含硬脂酸和壳聚糖或果胶修饰。使用人类腺癌细胞系Caco-2细胞模型进行体外评价bLf的细胞摄取和输运。载荷bLf的固体脂质颗粒在八小时内对细胞毒性无显著影响,并且未引发细胞凋亡。共聚焦激光扫描显微镜的使用证实bLf通过受体介导的内吞作用,而固体脂质颗粒的细胞摄取主要机制是内吞作用。与bLf相比,载荷bLf的固体脂质颗粒的细胞摄取明显增多,而这种影响因时间、温度和浓度而异。维拉帕米和EDTA都能提高bLf和载荷bLf的表观渗透系数(App),这是因为它们与P-糖蛋白相互作用,并具有促进渗透的影响。这些研究结果暗示着固体脂质颗粒可能存在一种额外的吸收机制,可能涉及Caco-2细胞中的P-糖蛋白转运蛋白介导的主动转运。这些结果表明,固体脂质颗粒有潜力成为有效的载体,提高蛋白质和多肽的口服生物利用度。
The aim of this project is to use pectin- and chitosan-modified solid lipid nanoparticles for bovine lactoferrin to enhance its cellular uptake and transport.Solid lipid particles containing bovine lactoferrin (bLf) were formulated through the solvent evaporation technique, incorporating stearic acid along with either chitosan or pectin modification. bLf cellular uptake and transport were evaluated in vitro using the human adenocarcinoma cell line Caco-2 cell model.The bLf-loaded SLPs showed no significant effect on cytotoxicity and did not induce apoptosis within the eight-hour investigation. The use of confocal laser scanning microscopy confirmed that bLf follows the receptor-mediated endocytosis, whereas the primary mechanism for the cellular uptake of SLPs was endocytosis. The bLf-loaded SLPs had significantly more cellular uptake compared to bLf alone, and it was observed that this impact varied based on the time, temperature, and concentration. Verapamil and EDTA were determined to raise the apparent permeability coefficients (App) of bLf and bLf-loaded SLPs.This occurred because they hindered efflux by interacting with P-glycoproteins and had a penetration-enhancing influence. These findings propose the possibility of an additional absorption mechanism for SLPs, potentially involving active transportation facilitated by the P-glycoprotein transporter in Caco-2 cells. These results suggest that SLPs have the potential to be applied as effective carriers to improve the oral bioavailability of proteins and peptides.