期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 460, 期 1-2, 页码 24-27出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2013.10.053
关键词
5-Fluorouracil; Folinic acid; Leucovorin; Iontophoresis; Buccal mucosa; Oral cancer
The objective was to investigate the feasibility of using buccal iontophoresis for the simultaneous delivery of chemotherapeutic agents with a view to developing a new approach to treat head and neck cancers. Short duration cathodal iontophoresis of 5-fluorouracil (5-FU; 20 mM) and leucovorin (LV; 10 mM) at 1 mA/cm(2) for 10 or 20 min from aqueous solution and a 2% hydroxyethyl cellulose gel at pH 7.6 was evaluated using bovine mucosa in vitro. Iontophoresis resulted in a statistically significant increase in the mucosal deposition of both drugs as compared to passive diffusion (Student's t-test, alpha = 0.05); in each case, drug delivery was selective for deposition with no permeation being observed. After 20 min of iontophoresis, there was an similar to 8-fold enhancement for 5-FU (1.46 +/- 0.86 and 11.93 +/- 3.81 mu g/cm(2), respectively) and a 3-fold increase for LV (8.31 +/- 2.44 and 25.08 +/- 6.89 mu g/cm(2), respectively) when using aqueous solutions. The same trend was observed when the gel was applied for 10 min; passive delivery of 5-FU from the gel resulted in non-detectable levels in the mucosa, while 4.62 +/- 1.76 mu g/cm(2) were deposited in the mucosa following iontophoresis. Similarly, iontophoretic delivery of LV from the gel resulted in similar to 3-fold higher deposition as compared to passive diffusion (6.71 +/- 1.36 and 21.12 +/- 9.94 mu g/cm(2), respectively). No drug permeation was observed in either case. In conclusion, iontophoresis can be used for targeted topical delivery of chemotherapeutics to the buccal mucosa and may enable less invasive local therapy of head and neck cancers. (C) 2013 Elsevier B.V. All rights reserved.
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