Yao Xudong, Bunt Craig, Liu Mengyang, Quek Siew-Young, Shaw John, Cornish Jillian, Wen Jingyuan
School of Pharmacy, Faculty of Medical and Health Science, The University of Auckland, Auckland 1142, New Zealand.
Department of Food Science, Otago University, Dunedin 9054, New Zealand.
Pharmaceutics. 2023 Aug 21;15(8):2168. doi: 10.3390/pharmaceutics15082168.
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.
本项目旨在使用果胶和壳聚糖修饰的固体脂质纳米粒来包裹牛乳铁蛋白，以增强其细胞摄取和转运能力。
采用溶剂蒸发技术制备含有牛乳铁蛋白（bLf）的固体脂质颗粒，并加入硬脂酸以及壳聚糖或果胶进行修饰。使用人腺癌细胞系Caco-2细胞模型在体外评估bLf的细胞摄取和转运情况。
负载bLf的固体脂质颗粒在八小时的研究中对细胞毒性无显著影响，也未诱导细胞凋亡。共聚焦激光扫描显微镜的使用证实bLf遵循受体介导的内吞作用，而固体脂质颗粒细胞摄取的主要机制是内吞作用。与单独的bLf相比，负载bLf的固体脂质颗粒具有显著更多的细胞摄取，并且观察到这种影响因时间、温度和浓度而异。维拉帕米和乙二胺四乙酸被确定可提高bLf和负载bLf的固体脂质颗粒的表观渗透系数（App）。
出现这种情况是因为它们通过与P-糖蛋白相互作用阻碍了外排，并具有渗透增强作用。这些发现提出了固体脂质颗粒存在额外吸收机制的可能性，可能涉及Caco-2细胞中P-糖蛋白转运体促进的主动转运。这些结果表明，固体脂质颗粒有潜力作为有效的载体来提高蛋白质和肽的口服生物利用度。
