College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China.
College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, China.
AAPS PharmSciTech. 2022 Aug 10;23(6):221. doi: 10.1208/s12249-022-02380-z.
β-Cyclodextrin (CD) and chitosan (CS) have attracted great attention due to their unique properties and structures. β-Cyclodextrin-grafted chitosan (CD-CS) has been widely used as a drug carrier to prepare nano-formulations for drug delivery. However, few researches have been conducted to investigate the effect of CD-CS as an excipient on cellular uptake and intestinal absorption. Herein, Caco-2 cells were used to investigate the influence of CD-CS on cellular uptake. The MTT assay showed that CD-CS was non-toxic to Caco-2 cells in concentrations ranging from 15.62 to 125 μg/mL. Confocal laser microscopy and flow cytometry measurements indicated that the uptake ability of Caco-2 cells was significantly enhanced after being treated with CD-CS at a concentration of 31.25 μg/mL or incubation for 0.5 h, and the uptake enhancement gradually increased with increasing CD-CS concentration and incubation time. The Caco-2 monolayer cell model and the everted intestinal sac method were employed to preliminarily explore the mechanism of the improved intestinal absorption. The results demonstrated that CD-CS might open the tight junctions and enhance the clathrin-dependent endocytosis, macro-pinocytosis, and phagocytosis of the intestinal epithelial cells. Such findings can serve as references and inspiration for the design of absorption enhancers.
β-环糊精（CD）和壳聚糖（CS）由于其独特的性质和结构而受到广泛关注。β-环糊精接枝壳聚糖（CD-CS）已被广泛用作药物载体，以制备用于药物传递的纳米制剂。然而，很少有研究探讨 CD-CS 作为赋形剂对细胞摄取和肠道吸收的影响。在此，我们使用 Caco-2 细胞来研究 CD-CS 对细胞摄取的影响。MTT 测定表明，在 15.62 至 125μg/mL 的浓度范围内，CD-CS 对 Caco-2 细胞没有毒性。共聚焦激光显微镜和流式细胞术测量表明，在浓度为 31.25μg/mL 或孵育 0.5h 后，Caco-2 细胞的摄取能力显著增强，并且摄取增强作用随着 CD-CS 浓度和孵育时间的增加而逐渐增加。我们使用 Caco-2 单层细胞模型和外翻肠囊法初步探讨了改善肠道吸收的机制。结果表明，CD-CS 可能打开紧密连接并增强肠上皮细胞的网格蛋白依赖性内吞作用、巨胞饮作用和吞噬作用。这些发现可以为吸收增强剂的设计提供参考和启示。
