| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2005: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥12,300,000 (Direct Cost: ¥12,300,000)
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| Research Abstract |
The absorption of erythropoietin (EPO), a representative non-absorbable drug, from the rat small intestine was confirmed by delivering EPO to the enterocytes with carbon nanotubes (CNT) after adsorbed with absorption enhancer, surfactant, as supramolecules. Although the superiority of CNT system was not observed in the case of a non-absorbable organic compound like gentamicin (GM), we succeeded to show the usefulness of CNT system as a carrier of oral DDS for protein drugs like EPO. CNT system containing EPO had a bioavailability of <1.0 % after small intestinal administration to rats. Many scientists have challenged the oral delivery of protein drugs using emulsion, liposomes, microcapsules and absorption enhancers and the reported bioavailability of protein drugs was at most several %. Our results on the absorption enhancing effect of CNT system on EPO suggest the advanced progress of oral delivery of protein drugs. However, it was made clear that the large variation of CNT between their production lot and their aggregation affect the absorption enhancing effect of CNT system. To accelerate the disaggregation of CNT, many procedures, cutting, dissolving, separation and purification, were used. It was found out that the short length CNT fibers less aggregate and had a strong absorption enhancing effect on EPO. When protease inhibitors, casein and lactoferrin, were added to CNT system to inhibit the hydrolytic enzymatic activity of proteases in the rat gastrointestinal tract, stability of EPO considerably increased and as a result higher bioavailability, 11 %, was obtained. From those results, the usefulness of CNT as a carrier of oral DDS has been suggested.
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