期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 601, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2021.120593
关键词
Intestinal permeation enhancers; Sucrose laurate ester; Oral peptide delivery; Ussing chamber; Intestinal epithelia; Caco-2 monolayers
资金
- Science Foundation Ireland's CURAM Centre for Medical Devices [13/RC/2073]
- European Regional Development Fund
The study compared the performance of three monoesters with varying sugar moieties as intestinal permeation enhancers. Results showed that all three esters enhanced permeability in rat intestinal tissue likely via tight junction modulation, while C12-trehalose was slightly less efficacious but also less damaging to the tissue. All three esters have potential for oral formulations as permeation enhancers.
Laurate (C12)-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: C12-sucrose, C12-lactose, and C12-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 (Papp) of [14C] mannitol across isolated rat intestinal mucosae, and tissue histology. For CMC, the rank order was C12-trehalose (0.21 mM) < C12sucrose (0.34 mM) < C12-lactose (0.43 mM). Exposure to Caco-2 cells for 120 min produced TC50 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 C12-trehalose was less potent. C12-sucrose and C12lactose increased the Papp of [14C] mannitol across mucosae with similar potency and efficacy, whereas C12trehalose 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 C12-sucrose and C12-lactose. In conclusion, the three esters enhanced permeability likely via tight junction modulation in rat intestinal tissue. C12-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.
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