Everted gut sac model as a tool in pharmaceutical research: limitations and applications

Alam, Mohammad Mumtaz; Al-Jenoobi, Fahad I.; Al-Mohizea, Abdullah M.

doi:10.1111/j.2042-7158.2011.01391.x

Cited by 162 publications

(115 citation statements)

References 111 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…Everted gut sacs were prepared as previously described. 18,19) Briefly, male rats were fasted overnight (approximately 18 h) before the experiment but had free access to water. After each rat was anesthetized with 1% pentobarbital sodium (4.0 mL/kg, intraperitoneal injection), a midline laparotomy was performed to expose the abdomen.…”

Section: Methodsmentioning

confidence: 99%

Permeability of Exendin-4-Loaded Chitosan Nanoparticles across MDCK Cell Monolayers and Rat Small Intestine

Wang

Zhang

Sun

et al. 2014

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

The purpose of this study was to investigate the permeability of exendin-4-loaded chitosan nanoparticles using the Madin Darby canine kidney (MDCK) cell monolayer as an in vitro model and the rat intestine as an ex vivo model of the human intestinal barrier. A series of formulations of sodium tripolyphosphate (TPP) and chitosan with different molecular weights and degrees of deacetylation was evaluated. The formulation consisting of 0.1% TPP and 0.2% chitosan (400 kDa, 95% degree of deacetylation), which gave optimized monodispersed particle size (303.1 10.36 nm), zeta potential (18.37 1.15 mV) and encapsulation efficiency (38.0 2.6%), was used for further analysis. After determining their biocompatibility, the transport potential of drug-loaded chitosan nanoparticles was evaluated and compared with free exendin-4 using both MDCK cell monolayers and different rat intestinal segments. Mechanisms underlying enhanced transport of exendin-4 in the cell model were also explored. Compared with free exendin-4, the absorption of optimized chitosan nanoparticles was enhanced by 4.7-fold in MDCK cell monolayers and by 2.0-2.78-fold in different rat intestinal segments, with no significant difference between the duodenum, jejunum and ileum. As supported by confocal laser scanning microscopic analysis, the lower enhancement of absorption in the intestine compared to the cell monolayer likely resulted from the chitosan nanoparticle-mediated opening of cellular tight junctions and not through intracellular transport. These findings suggest that the potential application of chitosan nanoparticles as delivery carriers of exendin-4 is limited and may need further modifications.

show abstract

Section: Methodsmentioning

confidence: 99%

Permeability of Exendin-4-Loaded Chitosan Nanoparticles across MDCK Cell Monolayers and Rat Small Intestine

Wang

Zhang

Sun

et al. 2014

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…The composition of the Krebs solution was 7 g/L sodium chloride, 0.34 g/L potassium chloride, 1.8 g/L glucose, 0.251 g/L disodium hydrogen phosphate, 0.207 g/L sodium dihydrogen phosphate, and 46.8 mg/L magnesium chloride. 18 Tween 80 1% was added to help enhance the wettability of the SLN, simulating the action of bile salts present in the biological intestinal medium. 19 Each segment was tied on one side with a braided silk suture, and 0.5 mL of the same medium containing a dispersed amount of sulpiride equivalent to 200 µg of the tested formulation was inserted using a 1 mL syringe.…”

Section: Intestinal Permeability Assessmentmentioning

confidence: 99%

“…Aliquots of 1 mL were withdrawn at certain time intervals and replaced with an equal fresh preheated aliquot at 37°C. 18,21 Samples were collected from the surrounding medium at 0.5, 1, 1.5, and 2 hours. The amount of drug transported through the intestinal segments was determined using HPLC.…”

Section: Intestinal Permeability Assessmentmentioning

confidence: 99%

Novel sulpiride-loaded solid lipid nanoparticles with enhanced intestinal permeability

Ibrahim¹,

Alomrani²,

Yassin³

2013

IJN

View full text Add to dashboard Cite

Background Solid lipid nanoparticles (SLN), novel drug delivery carriers, can be utilized in enhancing both intestinal permeability and dissolution of poorly absorbed drugs. The aim of this work was to enhance the intestinal permeability of sulpiride by loading into SLN. Methods A unique ultrasonic melt-emulsification method with minimum stress conditions was used for the preparation of SLN. The mixture of the drug and the melted lipids was simply dispersed in an aqueous solution of a surfactant at a temperature that was 10°C higher than the melting points of the lipids using probe sonication, and was then simultaneously dispersed in cold water. Several formulation parameters were optimized, including the drug-to-lipid ratio, and the types of lipids and surfactants used. The produced SLN were evaluated for their particle size and shape, surface charge, entrapment efficiency, crystallinity of the drug and lipids, and the drug release profile. The rat everted sac intestine model was utilized to evaluate the change in intestinal permeability of sulpiride by loading into SLN. Results The method adopted allowed successful preparation of SLN with a monodispersed particle size of 147.8–298.8 nm. Both scanning electron microscopic and atomic force microscopic images showed uniform spherical particles and confirmed the sizes determined by the light scattering technique. Combination of triglycerides with stearic acid resulted in a marked increase in zeta potential, entrapment efficiency, and drug loading; however, the particle size was increased. The type of surfactant used was critical for particle size, charge, drug loading, and entrapment efficiency. Generally, the in vitro release profile demonstrated by all formulations showed the common biphasic mode with a varying degree of burst release. The everted sac model showed markedly enhanced sulpiride permeability in the case of the SLN-loaded formulation. The in situ results showed a very good correlation with the in vitro release data. Conclusion Incorporation of sulpiride into SLN results in enhanced intestinal permeability of sulpiride, that may in turn increase overall oral absorption of the drug. The superior attributes of the prepared SLN, specifically the high particle size uniformity and drug loading capacity, is considered novel, especially given the simplicity and modest nature of the sonication method used.

show abstract

“…73 Isolated ex vivo intestinal tissue from rat and human has been tested with PEs in Ussing chambers, [74][75][76] as well as in everted rat gut sacs. 77 Although these systems account for villi, increased transporter expression and mucus secretion, they lack blood supply which assists complete mechanistic repair of damaged tissue. Barthe et al, recommend that the intestinal sac model cannot be relied upon for accurate flux data beyond 60 min, even when maintained in culture medium.…”

mentioning

confidence: 99%

Safety concerns over the use of intestinal permeation enhancers: A mini-review

2016

View full text Add to dashboard Cite

Intestinal permeation enhancers (PEs) are key components in »12 oral peptide formulations in clinical trials for a range of molecules, primarily insulin and glucagon-like-peptide 1 (GLP-1) analogs. The main PEs comprise medium chain fatty acid-based systems (sodium caprate, sodium caprylate, and N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC)), bile salts, acyl carnitines, and EDTA. Their mechanism of action is complex with subtle differences between the different molecules. With the exception of SNAC and EDTA, most PEs fluidize the plasma membrane causing plasma membrane perturbation, as well as enzymatic and intracellular mediator changes that lead to alteration of intestinal epithelial tight junction protein expression. The question arises as to whether PEs can cause irreversible epithelial damage and tight junction openings sufficient to permit co-absorption of payloads with bystander pathogens, lipopolysaccharides and its fragment, or exo-and endotoxins that may be associated with sepsis, inflammation and autoimmune conditions. Most PEs seem to cause membrane perturbation to varying extents that is rapidly reversible, and overall evidence of pathogen co-absorption is generally lacking. It is unknown however, whether the intestinal epithelial damage-repair cycle is sustained during repeat-dosing regimens for chronic therapy.

show abstract

Everted gut sac model as a tool in pharmaceutical research: limitations and applications

Cited by 162 publications

References 111 publications

Permeability of Exendin-4-Loaded Chitosan Nanoparticles across MDCK Cell Monolayers and Rat Small Intestine

Permeability of Exendin-4-Loaded Chitosan Nanoparticles across MDCK Cell Monolayers and Rat Small Intestine

Novel sulpiride-loaded solid lipid nanoparticles with enhanced intestinal permeability

Safety concerns over the use of intestinal permeation enhancers: A mini-review

Contact Info

Product

Resources

About