UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
School of Pharmacy, University of Camerino, Via Gentile III da Varano, 62032 Camerino, MC, Italy.
Int J Pharm. 2021 May 15;601:120593. doi: 10.1016/j.ijpharm.2021.120593. Epub 2021 Apr 20.
Laurate (C)-sucrose esters are established intestinal epithelial permeation enhancers (PEs) with potential for use in oral delivery. Most studies have examined blends of ester rather than specific monoesters, with little variation on the sugar moiety. To investigate the influence of varying the sugar moiety on monoester performance, we compared three monoesters: C-sucrose, C-lactose, and C-trehalose. The assays were: critical micellar concentration (CMC) in Krebs-Henseleit buffer, MTS and lactate dehydrogenase assays in Caco-2 cells, transepithelial electrical resistance (TEER) and apparent permeability coefficient (P) of [C] mannitol across isolated rat intestinal mucosae, and tissue histology. For CMC, the rank order was C-trehalose (0.21 mM) < C-sucrose (0.34 mM) < C-lactose (0.43 mM). Exposure to Caco-2 cells for 120 min produced TC values in the MTS assay from 0.1 to 0.4 mM. Each ester produced a concentration-dependent decrease in TEER across rat mucosae with 80% reduction seen with 8 mM in 5 min, but C-trehalose was less potent. C-sucrose and C-lactose increased the P of [C] mannitol across mucosae with similar potency and efficacy, whereas C-trehalose was not as potent or efficacious, even though it still increased flux. In the presence of the three esters, gross intestinal histology was unaffected except at 8 mM for C-sucrose and C-lactose. In conclusion, the three esters enhanced permeability likely via tight junction modulation in rat intestinal tissue. C-trehalose was not quite as efficacious, but neither did it damage tissue to the same extent. All three can be considered as potential PEs to be included in oral formulations.
laureate (C)-蔗糖酯是已确立的肠上皮渗透增强剂 (PEs)，具有用于口服递送的潜力。大多数研究都检查了酯的混合物而不是特定的单酯，糖部分的变化很小。为了研究改变糖部分对单酯性能的影响，我们比较了三种单酯：C-蔗糖、C-乳糖和 C-海藻糖。测定方法如下：Krebs-Henseleit 缓冲液中的临界胶束浓度 (CMC)、Caco-2 细胞中的 MTS 和乳酸脱氢酶测定、[C]甘露醇在分离的大鼠肠黏膜上的跨上皮电阻 (TEER)和表观渗透系数 (P)，以及组织病理学。对于 CMC，顺序为 C-海藻糖（0.21 mM）<C-蔗糖（0.34 mM）<C-乳糖（0.43 mM）。暴露于 Caco-2 细胞 120 分钟后，MTS 测定中的 TC 值在 0.1 至 0.4 mM 之间。每种酯都导致 TEER 在大鼠黏膜上呈浓度依赖性下降，8 分钟内 8 mM 时下降 80%，但 C-海藻糖的作用较弱。C-蔗糖和 C-乳糖均增加了[C]甘露醇穿过黏膜的 P，效力和功效相似，而 C-海藻糖的效力和功效都不如前两者，尽管它仍能增加通量。在三种酯的存在下，除了 8 mM 的 C-蔗糖和 C-乳糖外，肠道大体组织学没有受到影响。总之，这三种酯通过调节大鼠肠组织中的紧密连接增加了通透性。C-海藻糖的功效不如前两者，但对组织的损伤也没有那么大。这三种都可以被认为是潜在的 PEs，可被包含在口服制剂中。
