2007 年 53 巻 3 号 p. 275-281
Dalton's lymphoma ascites (DLA) cells were used as a model cell line to evaluate the cytotoxic concentration and anti-tumor activity of 5-fluorouracil (5-FU) through transdermal drug delivery (TDD) for solid tumors. Cytotoxicity was measured by exposing cell suspensions to increased concentrations of drug from 10-50 μg/ml and then the viable cells count was measured by the tryphan blue exclusion method. The results confirmed that 50 μg/ml of 5-FU was cytotoxic to DLA cells. The tumor volume was 0.23 cm2 and the increase in life span (ILS) was 81.8% with a maximum survival time of 39.5±1.87 days for 5-FU monolithic matrix transdermal patch in mice with solid tumors induced by DLA. The results were significantly different (p<0.05) compared to the untreated control, which had a maximum survival time of 19±1 days. The anti-tumor activity was very effective compared to intravenous therapy (ILS, 25.58%, maximum survival time, 24±2.7 days). No signs of erythema, vesiculations or bullous reaction were observed with the patches. The mean cumulative skin irritation and adherence scores for both mice and humans were zero and less than one, proving there was no irritation or sensitization. The patches adhered completely to the skin, without leaving any adhesive on skin (score=0 in human subjects). The transdermal patches had 100% flatness, a thickness of 150±0.03 mm, good content uniformity, folding endurance (>500 foldings), elegance, smoothness, transparency, and flexibility. The Velcro protection jackets were suitable for the study and prevented the mice from licking, scratching, and rubbing the patches.
