Influence of permeability enhancers on the paracellular permeability of metformin hydrochloride and furosemide across Caco-2 cells
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, cilt.101, sa.4, ss.185-199, 2023 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 101 Sayı: 4
- Basım Tarihi: 2023
- Doi Numarası: 10.1139/cjpp-2022-0265
- Dergi Adı: CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, SportDiscus, Veterinary Science Database
- Sayfa Sayıları: ss.185-199
- Hacettepe Üniversitesi Adresli: Evet
Özet
Permeability enhancers can affect absorption of paracellularly transported drugs. This study aims to evaluate effects of per-meability enhancers (chitosan, methyl-13-cyclodextrin, sodium caprate, sodium lauryl sulfate, etc.) on the permeability of para-cellularly absorbed furosemide and metformin hydrochloride. Methyl thiazole tetrazolium bromide test was carried out to de -termine the drug concentrations in permeability study. Trans-epithelial electrical resistance (TEER) values determined to assess the integrity of tight junctions. Permeability enhancers were applied at different concentrations alone, in dual/triple combina-tions. Permeability was determined using human colorectal adenocarcinoma (Caco-2) cells (TEER > 400 S2 center dot cm2). Permeability enhancers have no significant effect (<2-fold; p > 0.05) on the permeability of furosemide (1.80 x 10-5 + 4.55 x 10-7 cm/s); however, metformin permeability (1.36 x 10-5 + 1.25 x 10-6 cm/s) increased significantly (p < 0.05) with 0.3% and 0.5% (w/v) chitosan (2.0-and 2.7-fold, respectively), 1% methyl-13-cyclodextrin (w/v) (3.5-fold), 10 and 20 mu mol/L sodium caprate (2.2-and 2.8-fold, respectively), and 0.012% sodium lauryl sulfate (w/v) (1.9-fold). Furosemide permeability increased significantly (p < 0.05) with chitosan-sodium lauryl sulfate combination (1.7-fold), and all triple combinations (1.4-to 1.9-fold). Chitosan containing dual/triple combinations resulted in significant increase (p < 0.05) in metformin permeability (1.7 to 2.8-fold). All results indi-cated that absorption of furosemide and metformin can be improved by the combination of permeability enhancers. Therefore, it can be evaluated for the formulation of development strategies containing furosemide and metformin by the pharmaceutical industry.