Enhanced Intestinal Absorption of Insulin by Capryol 90, a Novel Absorption Enhancer in Rats: Implications in Oral Insulin Delivery
| Autor: | Akira Yamamoto, Hiroki Ukai, Kazuki Iwasa, Hidemasa Katsumi, Takamasa Deguchi, Masaki Morishita |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
insulin
tight junction medicine.medical_treatment Pharmaceutical Science Excipient lcsh:RS1-441 02 engineering and technology Pharmacology peptide absorption 030226 pharmacology & pharmacy Article Intestinal absorption lcsh:Pharmacy and materia medica 03 medical and health sciences 0302 clinical medicine Oral administration medicine absorption enhancer Caco-2 cells drug absorption Chemistry Insulin intestinal absorption 021001 nanoscience & nanotechnology Intestinal epithelium Small intestine medicine.anatomical_structure Caco-2 Paracellular transport 0210 nano-technology medicine.drug |
| Zdroj: | Pharmaceutics, Vol 12, Iss 462, p 462 (2020) Pharmaceutics Volume 12 Issue 5 |
| ISSN: | 1999-4923 |
| Popis: | Labrasol® is a self-emulsifying excipient that contains saturated polyglycolysed C6&ndash C14 glycerides and this additive is known to improve the intestinal absorption of poorly absorbed drugs after oral administration. However, the effects of formulations similar to Labrasol® on the intestinal absorption of poorly absorbed drugs have not been characterized. In this study, we used insulin as a model peptide drug and examined the absorption-enhancing effects of Labrasol® and its related formulations for insulin absorption in rats. The co-administration of Labrasol-related formulations with insulin reduced the blood glucose levels. Among these formulations, Capryol 90 was the most effective additive. Notably, the effect of Capryol 90 was greater at pH 3.0 than at pH 7.0. Additionally, almost no mucosal damage was observed in the presence of these formulations, as these formulations did not affect the activity of lactate dehydrogenase (LDH) and the amount of protein released from the small intestine. In mechanistic studies, Capryol 90 improved the stability of insulin and suppressed the association with insulin under acidic conditions. The loosening of the tight junctions (TJs) could be the underlying mechanism by which Capryol 90 improved intestinal insulin absorption via a paracellular route. These findings suggest that Capryol 90 is an effective absorption enhancer for improving the intestinal absorption of insulin, without inducing serious damage to the intestinal epithelium. |
| Databáze: | OpenAIRE |
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