scholarly journals Development of mucosal absorption enhancers used biopharmaceuticals

2020 ◽  
Vol 35 (1) ◽  
pp. 10-19
Author(s):  
Hideyuki Tamiwa ◽  
Mariko Takeda-Morishita
Keyword(s):  
Absorption Enhancers ◽  
Mucosal Absorption

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.

Transport Characteristics of Wheat Germ Agglutinin-Modified Insulin-Liposomes and Solid Lipid Nanoparticles in a Perfused Rat Intestinal Model

2006 ◽  
Vol 6 (9) ◽  
pp. 2959-2966 ◽  
Author(s):  
Na Zhang ◽  
Qineng Ping ◽  
Guihua Huang ◽  
Xiuzhen Han ◽  
Yanna Cheng ◽  
...  
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Wheat Germ Agglutinin ◽  
Wheat Germ ◽  
Serum Insulin ◽  
Lipid Nanoparticles ◽  
Solid Lipid ◽  
Mucosal Absorption ◽  
Perfusion Experiment ◽  
Absorption Sites

Wheat germ agglutinin (WGA) modified liposomes and solid lipid nanoparticles (SLNs) were evaluated for improving intestinal absorption of insulin. In an in situ local intestinal perfusion experiment, formulations containing 100 IU/kg insulin were administered to the duodenum, jejunum, and ileum of fasted rats. As hypothesized, ileum was the best intestinal location for the absorption of insulin-containing liposomes. Serum insulin concentrations decreased for the various formulations in different absorption sites according to the following trends: Duodenum > ileum > jejunum for WGA-modified insulin-containing liposomes; duodenum > jejunum > ileum for WGA-modified insulin-containing SLNs; ileum > jejunum > duodenum for insulin-containing liposomes; ileum > duodenum > jejunum for insulin-containing SLNs; and duodenum ≥ ileum > jejunum for aqueous solution of insulin. These results imply that the nanoparticle type and delivery site were important factors with respect to increasing the bioavailability of insulin following oral administration. The proteolytic degradation as well as the epithelial permeability were primary determinants influcing insulin mucosal absorption.

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 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

scholarly journals A claudin‐4 modulator enhances the mucosal absorption of peptide

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Hiroshi Uchida ◽  
Masuo Kondoh ◽  
Takeshi Hanada ◽  
Azusa Takahashi ◽  
Takao Hamakubo ◽  
...  
Keyword(s):  
Mucosal Absorption

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.

scholarly journals Nasal mucosal absorption of tetracosactrin as indicated by rise in plasma fluorogenic corticosteroids

BMJ ◽  
1969 ◽  
Vol 4 (5680) ◽  
pp. 407-408 ◽  
Author(s):  
J. Keenan ◽  
M. A. Chamberlain
Keyword(s):  
Mucosal Absorption
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