Vitamin B12-mediated uptake of erythropoietin and granulocyte colony stimulating factor in vitro and in vivo
| Autor: | Habberfield Alan D, Kathleen Jensen-Pippo, Lloyd D. Ralph, Steven William Westwood, Gregory John Russell-Jones |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Vitamin
medicine.medical_treatment Pharmaceutical Science Pharmacology Biology Epithelium In vitro Granulocyte colony-stimulating factor law.invention chemistry.chemical_compound medicine.anatomical_structure Cytokine Biochemistry chemistry In vivo law Erythropoietin medicine Recombinant DNA medicine.drug |
| Zdroj: | International Journal of Pharmaceutics. 145:1-8 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/s0378-5173(96)04690-x |
| Popis: | Proteins are normally very poorly absorbed from the intestine as the intestinal epithelial cells act as a barrier to the uptake of all but the smallest of molecules. We have used the natural uptake mechanism for Vitamin B 12 (VB 12 ) to increase the absorption of proteins from the gut. VB 12 was conjugated to two recombinant human therapeutic proteins, granulocyte colony stimulating factor (G-CSF) and erythropoietin (EPO). In an in vitro model of VB 12 uptake, high levels of VB 12 -G-CSF conjugates were shown to be transported across the epithelial cell monolayer when compared to free G-CSF. In in vivo experiments in rats, both VB 12 -EPO and VB 12 -G-CSF conjugates were transported into the circulation from the gut lumen. Uptake was sufficient to generate a therapeutic response in animals receiving VB 12 -G-CSF, but not in those administered G-CSF alone. These preliminary findings have important implications in the oral delivery of peptide and protein pharmaceuticals. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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