scholarly journals Therapeutic innovation and regulatory sciences for paracellular absorption enhancers for biologics

2020 ◽  
Vol 35 (1) ◽  
pp. 20-26
Author(s):  
Keisuke Tachibana ◽  
Masuo Kondoh
Keyword(s):  
Absorption Enhancers ◽  
Paracellular Absorption ◽  
Regulatory Sciences

Gastrointestinal Region Specific Insulin Permeation Enhancement by Aloe vera Gel

2020 ◽  
Vol 10 (2) ◽  
pp. 117-122
Author(s):  
Elizca Pretorius ◽  
Clarissa Willers ◽  
Josias H. Hamman ◽  
Johan D. Steyn
Keyword(s):  
Gastrointestinal Tract ◽  
Ex Vivo ◽  
Aloe Vera ◽  
Diffusion Chamber ◽  
Proximal Jejunum ◽  
Absorption Enhancers ◽  
Permeation Enhancement ◽  
Insulin Transport ◽  
Aloe Vera Gel ◽  
Specific Insulin

Background: The oral administration route is still the most preferred by patients for drug treatment, but is unfortunately not suitable for all drug compounds. For example, protein and peptide drugs (e.g. insulin) are typically administered via injection seeing as they are unstable in the gastrointestinal luminal environment and have poor membrane permeation properties. To overcome this problem, functional excipients such as drug absorption enhancers can be co-administered. Although Aloe vera gel has the ability to improve the permeation of drugs across the intestinal epithelium, its drug permeation enhancing effect has not been investigated in the different regions of the gastrointestinal tract yet. Objective: The aim of this study was to investigate the insulin permeation enhancing effects of A. vera gel material across excised pig intestinal tissues from different regions of the gastrointestinal tract and to identify the gastrointestinal region where the highest insulin permeation enhancement was achieved. : Insulin transport across excised pig intestinal tissues from the duodenum, proximal jejunum, medial jejunum, distal jejunum, ileum and colon was measured in the absence and presence of A. vera gel (0.5% w/v) using both the Sweetana-Grass diffusion chamber and everted sac techniques. Results: The insulin permeation results obtained from both ex vivo techniques showed varied permeation enhancing effects of A. vera gel as a function of the different regions of the gastrointestinal tract. The colon was identified as the gastrointestinal region where A. vera gel was the most effective in terms of insulin permeation enhancement in the Sweetana-Grass diffusion chamber technique with a Papp value of 5.50 x 10-7 cm.s-1, whereas the ileum was the region where the highest permeation enhancement occurred in the everted sac technique with a Papp value of 5.45 x 10-7 cm.s-1. Conclusion: The gastrointestinal permeation enhancing effects of A. vera gel on insulin is region specific with the highest effect observed in the ileum and colon.

Absorption Properties of Luteolin and Apigenin in Genkwa Flos Using In Situ Single-Pass Intestinal Perfusion System in the Rat

2017 ◽  
Vol 45 (08) ◽  
pp. 1745-1759 ◽  
Author(s):  
Xin He ◽  
Zi-Jing Song ◽  
Cui-Ping Jiang ◽  
Chun-Feng Zhang
Keyword(s):  
Small Intestine ◽  
Intestinal Absorption ◽  
Rat Model ◽  
Clinical Effectiveness ◽  
Intestinal Perfusion ◽  
Flower Bud ◽  
Transport Pathway ◽  
Absorption Enhancers ◽  
Single Pass

The flower bud of Daphne genkwa (Genkwa Flos) is a commonly used herbal medicine in Asian countries. Luteolin and apigenin are two recognized active flavonoids in Genkwa Flos. The aim of this study was to investigate the intestinal absorption mechanisms of Genkwa Flos flavonoids using in situ single-pass intestinal perfusion rat model. Using HPLC, we determined its major effective flavonoids luteolin, apigenin, as well as, hydroxygenkwanin and genkwanin in biological samples. The intestinal absorption mechanisms of the total flavonoids in Genkwa Flos (TFG) were investigated using in situ single-pass intestinal perfusion rat model. Comparing the TFG absorption rate in different intestinal segments, data showed that the small intestine absorption was significantly higher than that of the colon ([Formula: see text]). Compared with duodenum and ileum, the jejunum was the best small intestinal site for TFG absorption. The high TFG concentration (61.48[Formula: see text][Formula: see text]g/ml) yielded the highest permeability ([Formula: see text]). Subsequently, three membrane protein inhibitors (verapamil, pantoprazole and probenecid) were used to explore the TFG absorption pathways. Data showed probenecid, a multidrug resistance protein (or MRP) inhibitor, effectively enhanced the TFG absorption ([Formula: see text]). Furthermore, by comparing commonly used natural absorption enhancers on TFG, it was observed that camphor was the most effective. In Situ single-pass intestinal perfusion experiment shows that TFG absorption is much higher in the small intestine than in the colon, and the TFG is absorbed mainly via an active transport pathway with MRP-mediated efflux mechanism. Camphor obviously enhanced the TFG absorption, and this could be an effective TFG formulation preparation method to increase clinical effectiveness after Genkwa Flos administration. Our study elucidated the TFG absorption mechanisms, and provided new information for its formulation preparation.

Effect of absorption enhancers on the absorption of FD-4 as a poorly absorbable marker macromolecule from the liver surface in rats

2014 ◽  
Vol 24 (4) ◽  
pp. 386-389 ◽  
Author(s):  
T. Mine ◽  
H. Miyamoto ◽  
N. Yoshikawa ◽  
S. Fumoto ◽  
H. Sasaki ◽  
...  
Keyword(s):  
Absorption Enhancers ◽  
Liver Surface

scholarly journals The Na+/H+ exchanger isoform 3 is required for active paracellular and transcellular Ca2+ transport across murine cecum

2013 ◽  
Vol 305 (4) ◽  
pp. G303-G313 ◽  
Author(s):  
Juraj Rievaj ◽  
Wanling Pan ◽  
Emmanuelle Cordat ◽  
R. Todd Alexander
Keyword(s):  
Water Movement ◽  
Water Flux ◽  
Wild Type Mouse ◽  
Wild Type ◽  
Rt Pcr ◽  
Ussing Chambers ◽  
Voltage Clamps ◽  
Paracellular Absorption ◽  
Mouse Intestine

Intestinal calcium (Ca2+) absorption occurs via paracellular and transcellular pathways. Although the transcellular route has been extensively studied, mechanisms mediating paracellular absorption are largely unexplored. Unlike passive diffusion, secondarily active paracellular Ca2+ uptake occurs against an electrochemical gradient with water flux providing the driving force. Water movement is dictated by concentration differences that are largely determined by Na+ fluxes. Consequently, we hypothesized that Na+ absorption mediates Ca2+ flux. NHE3 is central to intestinal Na+ absorption. NHE3 knockout mice (NHE3−/−) display impaired intestinal Na+, water, and Ca2+ absorption. However, the mechanism mediating this latter abnormality is not clear. To investigate this, we used Ussing chambers to measure net Ca2+ absorption across different segments of wild-type mouse intestine. The cecum was the only segment with net Ca2+ absorption. Quantitative RT-PCR measurements revealed cecal expression of all genes implicated in intestinal Ca2+ absorption, including NHE3. We therefore employed this segment for further studies. Inhibition of NHE3 with 100 μM 5-( N-ethyl- N-isopropyl) amiloride decreased luminal-to-serosal and increased serosal-to-luminal Ca2+ flux. NHE3−/− mice had a >60% decrease in luminal-to-serosal Ca2+ flux. Ussing chambers experiments under altered voltage clamps (−25, 0, +25 mV) showed decreased transcellular and secondarily active paracellular Ca2+ absorption in NHE3−/− mice relative to wild-type animals. Consistent with this, cecal Trpv6 expression was diminished in NHE3−/− mice. Together these results implicate NHE3 in intestinal Ca2+ absorption and support the theory that this is, at least partially, due to the role of NHE3 in Na+ and water absorption.

scholarly journals Intestinal Absorption Profile of Three Polygala Oligosaccharide Esters in Polygalae Radix and the Effects of Other Components in Polygalae Radix on Their Absorption

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
YinYing Ba ◽  
MengLin Wang ◽  
KunFeng Zhang ◽  
QiJun Chen ◽  
JiaJia Wang ◽  
...  
Keyword(s):  
Future Research ◽  
Active Components ◽  
Sodium Caprate ◽  
P Glycoprotein ◽  
Paracellular Absorption ◽  
Underlying Mechanisms ◽  
The Relationship ◽  
Rat Gut ◽  
Human Nervous System

Oligosaccharide esters, which are among the main active components of Polygalae Radix (PR), demonstrate significant pharmacological activities in the human nervous system. In our previous research, some other constituents in PR were able to improve the bioavailability of oligosaccharide esters such as sibiricose A5 (SA5), sibiricose A6 (SA6), and 3,6′-disinapoyl sucrose (DISS), but the related components and their underlying mechanisms remain unknown. The present study aimed to investigate the intestinal absorptive profile of SA5, SA6, and DISS and the absorptive behavior influenced by the coadministration of polygalaxanthone III and total saponins of PR (TS) using an in vitro everted rat gut sac model, along with the possible mechanisms that may influence absorption. The results showed that TS could significantly enhance the absorption of SA5, SA6, and DISS monomers. Verapamil, a P-glycoprotein inhibitor, was able to elevate the absorption of SA5 and SA6, and an absorption experiment using Rho123 led us to conclude that TS influenced the absorption of SA5 and SA6 in a manner similar to that of a P-glycoprotein inhibitor. Sodium caprate, a paracellular absorption enhancer, was found to increase the absorption of SA5, SA6, and DISS. Results showed that the absorption mechanisms of SA5 and SA6 may combine active transport with paracellular passive penetration, while DISS’s absorption was dominated by paracellular passive penetration. However, the relationship between polygala saponins and the absorption of SA5, SA6, and DISS by paracellular passive penetration remain to be examined. This is the direction of our future research.

scholarly journals Effectiveness and Toxicity Screening of Various Absorption Enhancers Using Caco-2 Cell Monolayers.

1998 ◽  
Vol 21 (6) ◽  
pp. 615-620 ◽  
Author(s):  
Ying-Shu QUAN ◽  
Koji HATTORI ◽  
Ewa LUNDBORG ◽  
Takuya FUJITA ◽  
Masahiro MURAKAMI ◽  
...  
Keyword(s):  
Toxicity Screening ◽  
Absorption Enhancers ◽  
Cell Monolayers

The regulatory sciences for stem cell-based medicinal products

2014 ◽  
Vol 8 (2) ◽  
pp. 190-200 ◽  
Author(s):  
Bao-Zhu Yuan ◽  
Junzhi Wang
Keyword(s):  
Stem Cell ◽  
Medicinal Products ◽  
Regulatory Sciences

scholarly journals Mechanistic Studies on the Absorption-Enhancing Effects of Gemini Surfactant on the Intestinal Absorption of Poorly Absorbed Hydrophilic Drugs in Rats

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 170 ◽  
Author(s):  
Tammam Alama ◽  
Kosuke Kusamori ◽  
Masaki Morishita ◽  
Hidemasa Katsumi ◽  
Toshiyasu Sakane ◽  
...  
Keyword(s):  
Intestinal Absorption ◽  
Gemini Surfactant ◽  
Closed Loop ◽  
Intestinal Cell ◽  
Mechanistic Studies ◽  
High Potency ◽  
Absorption Enhancers ◽  
Hydrophilic Drugs ◽  
Loop Method

Generally, the use of absorption enhancers might be the most effective approaches to ameliorate the enteric absorption of poorly absorbed substances. Among numerous absorption enhancers, we already reported that a gemini surfactant, sodium dilauramidoglutamide lysine (SLG-30) with two hydrophobic and two hydrophilic moieties, is a novel and promising adjuvant with a high potency in improving the absorption safely. Here, we examined and elucidated the absorption-improving mechanisms of SLG-30 in the enteric absorption of substances. SLG-30 increased the intestinal absorption of 5(6)-carboxyfluorescein (CF) to a greater level than the typical absorption enhancers, including sodium glycocholate and sodium laurate, as evaluated by an in situ closed-loop method. Furthermore, SLG-30 significantly lowered the fluorescence anisotropy of dansyl chloride (DNS-Cl), suggesting that it might increase the fluidity of protein sections in the intestinal cell membranes. Moreover, SLG-30 significantly lowered the transepithelial-electrical resistance (TEER) values of Caco-2 cells, suggesting that it might open the tight junctions (TJs) between the enteric epithelial cells. Additionally, the levels of claudin-1 and claudin-4 expression decreased in the presence of SLG-30. These outcomes propose that SLG-30 might improve the enteric transport of poorly absorbed substances through both transcellular and paracellular routes.

Sign in / Sign up

Export Citation Format

Share Document