scholarly journals Preparation of nobiletin in self-microemulsifying systems and its intestinal permeability in rats

2008 ◽  
Vol 11 (3) ◽  
pp. 22 ◽  
Author(s):  
Jing Yao ◽  
Yun Lu ◽  
Jian Ping Zhou
Keyword(s):  
Intestinal Permeability ◽  
Drug Delivery Systems ◽  
Effective Permeability ◽  
Statistical Difference ◽  
Oral Absorption ◽  
Intestinal Transport ◽  
Intestinal Perfusion ◽  
Single Pass ◽  
Intestinal Segments ◽  
Transit Model

ABSTRACT: PURPOSE. The objective of this study was to prepare nobiletin self-microemulsifying drug delivery systems (SMEDDS) and investigate its intestinal transport behavior using the single-pass intestinal perfusion (SPIP) method in rat. METHODS. The characterizations of nobiletin SMEDDS were investigated. SPIP was performed in each isolated region of the small intestine (i.e. duodenum, jejunum, ileum and colon) over three concentrations of nobiletin (15, 30 and 60 µg/ml) at a flow rate of 0.2 ml/min. The concentrations of the samples were determined by HPLC and the effective permeability coefficients (Peff) in rats were calculated. Considering the high correlation of rat Peff values with those of human, the human intestinal permeability was predicted using the Lawrence compartment absorption and transit model. The intestinal permeability of nobiletin in SMEDDS, sub-microemulsion and micelles was compared. RESULTS. The particle size and zeta potential of nobiletin SMEDDS were (28.6±0.3) nm and (–22.6±3.5) mV, respectively. The Peff in jejunum at 15 µg/ml was significantly higher than that at 60 µg/ml (p< 0.01). The Peff in colon was higher at the same concentration comparing to the other intestinal segments. Moreover, there was no statistical difference in Peff at each same concentration in jejunum, duodenum and ileum. The estimated human absorption of nobiletin for the SMEDDS dilutions was higher than that for sub-microemulsions (p0.05). CONCLUSIONS. Bases on the above results, the SMEDDS could enhance the intestinal permeability of the nobiletin, and may be presented as potential candidates for improving the oral absorption of the noblietin. KEYWORDS. Nobiletin; Single-pass intestinal perfusion; Self-microemulsifying; Intestinal permeability

Intestinal transport of HDND-7, a novel hesperetin derivative, in in vitro MDCK cell and in situ single-pass intestinal perfusion models

Xenobiotica ◽  
2016 ◽  
Vol 47 (8) ◽  
pp. 719-730 ◽  
Author(s):  
Ruonan Chen ◽  
Lan Li ◽  
Chenlin Shen ◽  
Cheng Huang ◽  
Taotao Ma ◽  
...  
Keyword(s):  
Mdck Cell ◽  
Intestinal Transport ◽  
Intestinal Perfusion ◽  
Single Pass

scholarly journals Intestinal Absorption Mechanisms of Five Flavonoids from Malus hupehensis (Pamp.) Rehd. Extracts in Situ Single-Pass Intestinal Perfusion and in Vitro Caco-2 Cell Model

2020 ◽  
Author(s):  
Hui Yang ◽  
Zhishu Tang ◽  
Jiangxue Cheng ◽  
Jing Wang ◽  
Junbo Zou ◽  
...  
Keyword(s):  
Cell Model ◽  
Paracellular Pathway ◽  
Intestinal Perfusion ◽  
Cancer Resistance ◽  
Absorption Mechanism ◽  
Single Pass ◽  
Malus Hupehensis ◽  
Intestinal Segments

Abstract Background: Previous studies have shown that Malus hupehensis (Pamp.) Rehd. extracts have anti-oxidant, anti-aging and other effects, its bioavailability is low, however its absorption mechanism is still unclear. To investigate the absorption properties of hyperin, quercitrin, phloridzin, quercetin, and phloretin in total flavonoids of Malus hupehensis (Pamp.) Rehd. Extracts. Methods: In situ single-pass intestinal perfusion model and in vitro Caco-2 cell model were used in this study. The effects of concentration of the extract, administration time, temperature, different intestinal segments, paracellular pathway were analyzed, and the effect of efflux inhibitors, such as the P-gp inhibitor verapamil, the multidrug resistance protein2 (MRP2) inhibitor indomethacin, the breast cancer resistance protein (BCRP) inhibitor reserpine, on the transport were evaluated. As well as EDTA, a tight junction regulator, was studied.Results: The results indicated that the jejunum was the optimal absorption intestine segment of quercitrin, phloridzin, and phloretin. And the greatest absorption intestine segment of quercetin was ileum. Furthermore, it was found that the absorption mechanisms of phloridzin in extract was involved in passive diffusion and the mediation of P-gp and MRP2 should not be neglected. The absorption mechanisms of quercetin and phloretin from extract involved active transport and were accompanied by the participation of efflux transporters, such as P-gp, MRP2 and BCRP. And also the paracellular pathway was involved in hyperin and quercitrin. Conclusion: The absorption mechanisms of five flavonoids from Malus hupehensis (Pamp.) Rehd. extract are related to the concentration of the drugs, intestinal segments, and efflux protein.

scholarly journals Regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 242 ◽  
Author(s):  
David Dahlgren ◽  
Maria-Jose Cano-Cebrián ◽  
Tobias Olander ◽  
Mikael Hedeland ◽  
Markus Sjöblom ◽  
...  
Keyword(s):  
Intestinal Permeability ◽  
Large Intestine ◽  
Ethylenediaminetetraacetic Acid ◽  
Sodium Dodecyl ◽  
Intestinal Perfusion ◽  
Permeation Enhancers ◽  
Drug Permeability ◽  
Colonic Absorption ◽  
Single Pass ◽  
Perfusion Model

Sufficient colonic absorption is necessary for all systemically acting drugs in dosage forms that release the drug in the large intestine. Preclinically, colonic absorption is often investigated using the rat single-pass intestinal perfusion model. This model can determine intestinal permeability based on luminal drug disappearance, as well as the effect of permeation enhancers on drug permeability. However, it is uncertain how accurate the rat single-pass intestinal perfusion model predicts regional intestinal permeability and absorption in human. There is also a shortage of systematic in vivo investigations of the direct effect of permeation enhancers in the small and large intestine. In this rat single-pass intestinal perfusion study, the jejunal and colonic permeability of two low permeability drugs (atenolol and enalaprilat) and two high-permeability ones (ketoprofen and metoprolol) was determined based on plasma appearance. These values were compared to already available corresponding human data from a study conducted in our lab. The colonic effect of four permeation enhancers—sodium dodecyl sulfate, chitosan, ethylenediaminetetraacetic acid (EDTA), and caprate—on drug permeability and transport of chromium EDTA (an established clinical marker for intestinal barrier integrity) was determined. There was no difference in jejunal and colonic permeability determined from plasma appearance data of any of the four model drugs. This questions the validity of the rat single-pass intestinal perfusion model for predicting human regional intestinal permeability. It was also shown that the effect of permeation enhancers on drug permeability in the colon was similar to previously reported data from the rat jejunum, whereas the transport of chromium EDTA was significantly higher (p < 0.05) in the colon than in jejunum. Therefore, the use of permeation enhancers for increasing colonic drug permeability has greater risks than potential medical rewards, as indicated by the higher permeation of chromium EDTA compared to the drugs.

scholarly journals Effect of Berbamine Hydrochloride on Absorption Parameters of Berberine Hydrochloride Based on in Situ Single-Pass Intestinal Perfusion System in the Rat

2020 ◽  
Author(s):  
Jie Gao ◽  
Hui Feng ◽  
Ruohong Bi ◽  
Lin Pan ◽  
Yi Shi ◽  
...  
Keyword(s):  
Mass Concentration ◽  
Concentration Ratio ◽  
Calcium Influx ◽  
Intestinal Perfusion ◽  
Control Group ◽  
Drug Bioavailability ◽  
Berberine Hydrochloride ◽  
Single Pass ◽  
Intestinal Segments

Abstract Background:Berberine is a kind of chemical that has obvious effects of lowering blood sugar, lowering blood lipid. The high toxicity of intravenous administration of berberine hydrochloride(BBH), it is only used for oral administration in clinic,but it only about 10% bioavailability. P-glycoprotein (P-gp) efflux function affects drug bioavailability，BBH is the substrate of P-gp, furthermore the recognized inhibitor of P-gp (such as verapamil) can promote the absorption of BBH. Berbamine hydrochloride(BAH) had a significant inhibitory effect on calcium influx after activation of receptor regulated calcium channels, and the calcium antagonistic effect of BAH is similar to that of verapamil. Methods: Based on the in situ single-pass intestinal perfusion method, this article compares the absorption of the BAH ratio group and the BBH control group in different intestinal segments,and investigates their absorption parameters. Results:The results of in situ single-pass intestinal perfusion showed that the absorption rate constant (Ka), effective permeability coefficient (Papp) , and cumulative absorption per unit area per hour (Q) in the duodenum, jejunum and ileum of the BAH ratio group were greater than those of the BBH control group, which means that the absorption of BBH in the ratio group increased in various intestinal segments, and the absorption of BBH in the small intestine was promoted by BAH.In addition,the mass concentration ratio of BBH and BAH group is B40:A50, B30:A20，where BBH is better absorbed than other groups. Conclusions:BAH can indeed promote the absorption of BBH,and improve the biological utilization of BBH degree.The mass concentration ratio of BBH and BAH group is B40:A50, B30:A20，where BBH is better absorbed than other groups, providing a basis for the development and research of the subsequent preparation of BBH.

Single-pass intestinal perfusion to establish the intestinal permeability of model drugs in mouse

2012 ◽  
Vol 436 (1-2) ◽  
pp. 472-477 ◽  
Author(s):  
Elvira Escribano ◽  
Xavier García Sala ◽  
Jorge Salamanca ◽  
Claudia Roig Navarro ◽  
Josep Queralt Regué
Keyword(s):  
Intestinal Permeability ◽  
Intestinal Perfusion ◽  
Single Pass
Sign in / Sign up

Export Citation Format

Share Document