Comparison of the lymphatic transport of a lipophilic drug from vehicles containing α-tocopherol and/or triglycerides in rats

Abstract

The applicability of alpha-tocopherol as a lymphotropic carrier for a highly lipophilic drug has been evaluated. Transport to the intestinal lymph of the highly lipophilic model drug, Lu28-179, in rats after administration to the stomach in an alpha-tocopherol emulsion was compared with lymphatic transport after administration of a sesame oil emulsion and an alpha-tocopherol/sesame oil emulsion. Lymphatic transport of the triglycerides and of alpha-tocopherol was determined. A conscious rat model was used, and the mesenteric lymph was collected. There was no significant difference between the cumulative masses of triglyceride from the two emulsions containing triglyceride 24 h after administration. Administration of an alpha-tocopherol emulsion seemed to induce mobilization of endogenous triglyceride. The lymphatic transport of alpha-tocopherol was less than 1 mg 24 h after administration of both emulsions containing alpha-tocopherol. The absorption of Lu28-179 from the alpha-tocopherol emulsion was very low, with a lymphatic recovery of 0.05%. When administered in an alpha-tocopherol/sesame oil emulsion, the recovery of Lu28-179 increased sevenfold to 0.35%. However, after administration of Lu28-179 in a sesame oil emulsion, the lymphatic recovery increased a further 13-fold to 4.5%. In conclusion, the study showed that alpha-tocopherol did not promote lymphatic absorption of Lu28-179 and thus was not a good lymphotropic carrier, as compared with sesame oil. Alpha-tocopherol in combination with sesame oil was not a good lymphotropic carrier either. The non-absorbed alpha-tocopherol fraction in the intestine might be able to prevent the absorption of Lu28-179.

Modeling Kinetics of Subcellular Disposition of Chemicals

“…[148][149][150] These compounds may also exhibit slow absorption into the blood and lymph capillaries in the villi, and enter the lymph via endocytosis in the Peyer's patches in ileum, especially in lipid-based formulations. [151][152][153][154][155][156][157][158][159][160] Absorption mostly proceeds by the transcellular route, with the molecules crossing epithelia and other tissues by passive and active transport through the bilayers and cell interiors. An exception is the absorption through the skin, where the only cells in the external stratum corneum layer are keratinized corneoytes.…”

“…In higher organisms, the first step is absorption , which brings the molecules from the point of entry or the site of administration into the bloodstream or the lymphatic system. Although the lymph circulation is much slower than that of the blood, very lipophilic chemicals may use the former route for distribution, piggy-backing on the transport systems of lipophilic nutrients. – These compounds may also exhibit slow absorption into the blood and lymph capillaries in the villi, and enter the lymph via endocytosis in the Peyer’s patches in ileum, especially in lipid-based formulations. – …”

Structural Characterisation and Dehydration Behaviour of Siramesine Hydrochloride

“…Lipid formulations6, 7 and solid dispersions8 have been prepared and pro‐drugs of the free base have been synthesised and evaluated 9. Furthermore, the drug has been used to investigate solubilisation and lymphatic transport of lipophilic drugs 10, 11. However, the crystal structures and the solid state characterisation of the hydrochloride salt and its recently discovered corresponding monohydrate have not been reported before.…”