Enhancing the Furosemide Permeability by Papain Minitablets Through a Triple Co-culture In Vitro Intestinal Cell Model

Corazza, Fulvio Gabriel; Ernesto, Júlia Vaz; Nambu, Felipe Augusto Nery; Calixto, Leandro Augusto; Varca, Gustavo H.C.; Vieira, Daniel Perez; Leite-Silva, Vânia Rodrigues; Andréo-Filho, Newton; Lopes, Patrícia Santos

doi:10.1208/s12249-020-01796-9

Cited by 3 publications

(3 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…26,27 This mechanism can likely facilitate not only the absorption of other larger molecules but also that of papain itself. 23 Papain has been recently increasingly used as a permeation promoter of various active compounds, 28 such as furosemide 29 or vancomycin, 30 as it significantly enhances oral bioavailability of these drugs without being cytotoxic. There is also stable evidence that cysteine proteases of plant origin are readily absorbed from the gastrointestinal tract in their active form after oral administration.…”

Section: Discussionmentioning

confidence: 99%

Region‐specific effects of the cysteine protease papain on gastric motility

Annaházi

Schröder

Schemann

2021

Neurogastroenterology Motil

View full text Add to dashboard Cite

Background: Papaya is a traditional remedy for gastrointestinal complaints in the folk medicine. On this basis, papain, a cysteine protease of the fruit, is sold as a nutritional supplement, although scientific data on its effects in the gastrointestinal tract are lacking. We aimed to explore the effect of papain on gastric motility in vitro.Methods: Guinea pig antrum and corpus strips were mounted in organ bath. Key results:Papain reversibly increased the amplitude of ongoing phasic contractions in both circular and longitudinal antrum strips without having an effect on the frequency or on the muscle tone. All three tested doses of papain (end cc.: 12.5 mg L −1 , 50 mg L −1 , 100 mg L −1 ) were similarly effective. Contrarily, in the corpus circular and longitudinal muscle strips, papain caused a dose-dependent relaxation, which was preceded by a transient contraction in most tissues. The effect was resistant to tetrodotoxin (1 µM), but diminished by the cysteine protease inhibitor E64 (4.5 µM) in both regions. In the corpus, L-NAME (100 µM) and the protease-activated receptor (PAR)-1 antagonist SCH79797 (5 µM) or the PAR-2 antagonist GB 83 (3 µM) did not change the effect of papain significantly. This demonstrates that the effects of papain are not neurally mediated and nitrergic pathways are not involved in the mechanism. The effects are linked to the enzymatic activity, but not executed via PAR-1 or 2. Conclusions and inferences:Papain alters gastric motility in a region-specific manner, which could at least partly explain its claimed beneficial effects in functional gastrointestinal disorders.

show abstract

Section: Discussionmentioning

confidence: 99%

Region‐specific effects of the cysteine protease papain on gastric motility

Annaházi

Schröder

Schemann

2021

Neurogastroenterology Motil

View full text Add to dashboard Cite

show abstract

“…Interestingly, Corazza et al evaluated the safety of papain and the formulation of native papain minitablets to promote in vitro permeation of furosemide through an innovative biomimetic triple coculture model of caco-2, HT29-MTX, and Raji cells. 118 Meantime, spheroids are also adopted in toxicological analysis. Arslan et al developed a robust 3D endocervix model to identify the physiological responses of steroid hormones.…”

Section: Ive Systems In Food Toxicology Analysismentioning

confidence: 99%

“…Papain is a plant-derived enzyme that can be used as a permeation promoter of active compounds. Interestingly, Corazza et al evaluated the safety of papain and the formulation of native papain minitablets to promote in vitro permeation of furosemide through an innovative biomimetic triple coculture model of caco-2, HT29-MTX, and Raji cells . Meantime, spheroids are also adopted in toxicological analysis.…”

Section: Ive Systems In Food Toxicology Analysismentioning

confidence: 99%

Exploitation of In Vivo-Emulated In Vitro System in Advanced Food Science

et al. 2023

J. Agric. Food Chem.

View full text Add to dashboard Cite

Reasonable model construction contributes to the accuracy of experimental results. Multiple in vivo models offer reliable choices for effective evaluation, whereas their applications are hampered due to adverse features including high time-consumption, high cost and ethical contradictions. In vivo-emulated in vitro systems (IVE systems) have experienced rapid development and have been brought into food science for about two decades. IVE systems’ flexibly gathers the strengths of in vitro and in vivo models into one, reflecting the results in an efficient, systematic and interacted manner. In this review, we comprehensively reviewed the current research progress of IVE systems based on the literature published in the recent two decades. By categorizing the IVE systems into 2D coculture models, spheroids and organoids, their applications were systematically summarized and typically exemplified. The pros and cons of IVE systems were also thoroughly discussed, drawing attention to present challenges and inspiring potential orientation and future perspectives. The wide applicability and multiple possibilities suggest IVE systems as an effective and persuasive platform in the future of advanced food science.

show abstract

Influence of permeability enhancers on the paracellular permeability of metformin hydrochloride and furosemide across Caco-2 cells

Gülsün

Izat

Şahin

2023

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

Permeability enhancers can affect absorption of paracellularly transported drugs. This study aims to evaluate effects of permeability enhancers (chitosan, methyl-β-cyclodextrin, sodium caprate, sodium lauryl sulfate) on the permeability of paracellularly absorbed furosemide and metformin hydrochloride. Methyl thiazole tetrazolium bromide test was carried out to determine the drug concentrations in permeability study. Trans-epithelial Electrical Resistance values determined to assess the integrity of tight junctions. Permeability enhancers were applied at different concentrations alone, in dual/triple combinations. Permeability was determined using human colorectal adenocarcinoma (Caco-2) cells (TEER>400 ohm.cm2). Permeability enhancers have no significant effect (<2-fold; p>0.05) on the permeability of furosemide (1.80x10-5±4.55x10-7 cm/s), however metformin permeability (1.36x10-5±1.25x10-6 cm/s) increased significantly (p<0.05) with 0.3%,0.5% (w/v) chitosan (2.0, 2.7-fold, respectively), 1% methyl-β-cyclodextrin (3.5-fold), 10 and 20 µM sodium caprate (2.2, 2.8-fold, respectively), and 0.012% sodium lauryl sulfate (1.9-fold). Furosemide permeability increased significantly (p<0.05) with chitosan-sodium lauryl sulfate combination (1.7-fold), and all triple combinations (1.4-1.9-fold). Chitosan containing dual/triple combinations resulted significant increase (p<0.05) in metformin permeability (1.7-2.8-fold). All results indicated that absorption of furosemide and metformin can be improved by the combination permeability enhancers. Therefore, it can be evaluated for formulation development strategies containing furosemide and metformin by pharmaceutical industry.

show abstract

Enhancing the Furosemide Permeability by Papain Minitablets Through a Triple Co-culture In Vitro Intestinal Cell Model

Cited by 3 publications

References 60 publications

Region‐specific effects of the cysteine protease papain on gastric motility

Region‐specific effects of the cysteine protease papain on gastric motility

Exploitation of In Vivo-Emulated In Vitro System in Advanced Food Science

Influence of permeability enhancers on the paracellular permeability of metformin hydrochloride and furosemide across Caco-2 cells

Contact Info

Product

Resources

About