Development of imiquimod-loaded mucoadhesive films for oral dysplasia

作者：Ramineni Sandeep K; Cunningham Larry L Jr; Dziubla Thomas D; Puleo David A^*

来源：Journal of Pharmaceutical Sciences, 2013, 102(2): 593-603.

DOI：10.1002/jps.23386

• oral cancer
• mucosal drug delivery
• biomaterials
• polyvinylpyrrolidone
• carboxymethylcellulose
• 2-hydroxypropyl-ss-cyclodextrin
• controlled release
• delivery
• polymeric drug carrier
• solubility

Oral squamous dysplasia, which can usually be readily visualized as leukoplakia during an oral examination and confirmed by histology, is often considered a premalignant condition. Current treatments, however, focus on the final stages of disease, and treatments such as surgery can lead to postoperative disabilities. Hence, this study was designed to develop a noninvasive, mucoadhesive drug delivery system loaded with an immune response modifier, imiquimod, as a treatment for precancerous dysplastic lesions. Blends of polyvinylpyrrolidone and carboxymethylcellulose were used to prepare mucoadhesive films that were backed with poly(ethylene-co-vinyl acetate). Because of the hydrophobic nature of imiquimod, four loading methods (sonication, linoleic acid, 2-hydroxypropyl-beta-cyclodextrin, and acetate buffer) were compared. The formation of imiquimodcyclodextrin complexes and their solubility was studied by differential scanning calorimetry and phase solubility studies. All films achieved sustained release of drug for 3 h except those prepared by linoleic acid. The high solubility of imiquimod in acetate buffer facilitated high loading capacity and greater release (68%) of drug than did the other formulations (approximately 40%). In summary, a noninvasive and local approach with the potential to treat precancerous lesions may be achieved by this described mucoadhesive drug delivery system.

• 出版日期2013-2