In Situ Perfusion System for Oral Mucosal Absorption in Dogs

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.

Download Full-text

Oleacein Intestinal Permeation and Metabolism in Rats Using an In Situ Perfusion Technique

Pharmaceutics ◽

10.3390/pharmaceutics13050719 ◽

2021 ◽

Vol 13 (5) ◽

pp. 719

Author(s):

Anallely López-Yerena ◽

Maria Pérez ◽

Anna Vallverdú-Queralt ◽

Eleftherios Miliarakis ◽

Rosa M. Lamuela-Raventós ◽

...

Keyword(s):

Intestinal Permeability ◽

Model Compound ◽

Virgin Olive Oil ◽

Extra Virgin Olive Oil ◽

Perfusion Technique ◽

In Situ Perfusion ◽

First Pass ◽

Health Promoting ◽

Intestinal Permeation

Oleacein (OLEA) is one of the most important phenolic compounds in extra virgin olive oil in terms of concentration and health-promoting properties, yet there are insufficient data on its absorption and metabolism. Several non-human models have been developed to assess the intestinal permeability of drugs, among them, single-pass intestinal perfusion (SPIP), which is commonly used to investigate the trans-membrane transport of drugs in situ. In this study, the SPIP model and simultaneous luminal blood sampling were used to study the absorption and metabolism of OLEA in rats. Samples of intestinal fluid and mesenteric blood were taken at different times and the ileum segment was excised at the end of the experiment for analysis by LC–ESI–LTQ–Orbitrap–MS. OLEA was mostly metabolized by phase I reactions, undergoing hydrolysis and oxidation, and metabolite levels were much higher in the plasma than in the lumen. The large number of metabolites identified and their relatively high abundance indicates an important intestinal first-pass effect during absorption. According to the results, OLEA is well absorbed in the intestine, with an intestinal permeability similar to that of the highly permeable model compound naproxen. No significant differences were found in the percentage of absorbed OLEA and naproxen (48.98 ± 12.27% and 43.96 ± 7.58%, respectively).

Download Full-text