Absorption-Enhancing Mechanisms of Capryol 90, a Novel Absorption Enhancer, for Improving the Intestinal Absorption of Poorly Absorbed Drugs: Contributions to Trans- or Para-Cellular Pathways.
Alendronate
/ metabolism
Animals
Caco-2 Cells
Claudin-4
/ metabolism
Dextrans
/ metabolism
Electric Impedance
Fluorescein-5-isothiocyanate
/ analogs & derivatives
Fluoresceins
/ metabolism
Humans
Intestinal Absorption
/ drug effects
Intestinal Mucosa
/ drug effects
Male
Membrane Fluidity
/ drug effects
Occludin
/ metabolism
Polymers
/ pharmacology
Propylene Glycols
/ pharmacology
Rats, Wistar
Tight Junctions
/ drug effects
Zonula Occludens-1 Protein
/ metabolism
Caco-2 cells
absorption enhancer
intestinal absorption
membrane fluidity
tight junction
Journal
Pharmaceutical research
ISSN: 1573-904X
Titre abrégé: Pharm Res
Pays: United States
ID NLM: 8406521
Informations de publication
Date de publication:
23 Nov 2020
23 Nov 2020
Historique:
received:
24
08
2020
accepted:
26
10
2020
entrez:
24
11
2020
pubmed:
25
11
2020
medline:
5
8
2021
Statut:
epublish
Résumé
We have previously reported that Capryol 90 improves the intestinal absorption of insulin, a peptide drug, without causing serious damage to the intestinal epithelium. However, the effects of Capryol 90 and its related formulations on the intestinal absorption of other drugs, and their absorption-enhancing mechanisms are still unclear. The aim of this study is to evaluate the effects of Capryol 90 and its related formulations on the intestinal absorption of drugs and elucidate their absorption-enhancing mechanisms. The intestinal absorption of 5(6)-carboxyfluorescein, fluorescein isothiocyanate-dextrans, and alendronate was evaluated using an in situ closed loop method. Brush border membrane vesicles (BBMVs) were labeled with fluorescent probes, and the fluidity of membrane was evaluated by a fluorescence depolarization method. The expression levels of tight junction (TJ) proteins were measured using a Western blot method and immunofluorescence staining. Among the tested excipients, Capryol 90 significantly improved the small and large intestinal absorption of drugs. In mechanistic studies, Capryol 90 increased the membrane fluidity of lipid bilayers in BBMVs. Additionally, Capryol 90 decreased the expression levels of TJ-associated proteins, namely claudin-4, occludin, and ZO-1. Capryol 90 is an effective absorption enhancer for improving the intestinal absorption of poorly absorbed drugs via both transcellular and paracellular pathways.
Identifiants
pubmed: 33230672
doi: 10.1007/s11095-020-02963-0
pii: 10.1007/s11095-020-02963-0
doi:
Substances chimiques
Claudin-4
0
Dextrans
0
Fluoresceins
0
Occludin
0
Ocln protein, rat
0
Polymers
0
Propylene Glycols
0
Tjp1 protein, rat
0
Zonula Occludens-1 Protein
0
capryol propylene glycol monocaprylate
0
fluorescein isothiocyanate dextran
0
6-carboxyfluorescein
3301-79-9
Fluorescein-5-isothiocyanate
I223NX31W9
Alendronate
X1J18R4W8P
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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