Development of Imiquimod-Loaded Mucoadhesive Films for Oral Dysplasia

Abstract

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 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 methods of loading (sonication, linoleic acid, 2-hydroxypropyl-β-cyclodextrin, and acetate buffer) were compared. The formation of imiquimod-cyclodextrin complexes and their solubility was studied by differential scanning calorimetry and phase solubility studies. All films achieved sustained release of drug for three hours except for those prepared by linoleic acid. The high solubility of imiquimod in acetate buffer facilitated high loading capability 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.

Competing properties of mucoadhesive films designed for localized delivery of imiquimod

“…Although previous work showed that 1:2 PVP:CMC mucoadhesive films lasted 4 hr submerged in sink conditions in vitro and achieved sustained release for up to 3 hr, 7 several other film properties were not reported, such as adhesiveness of film to mucosal surface, mechanical properties for better handling, and swelling, which determines the release mechanism. All of these characteristics will play key roles in the design of a successful, bioerodible, mucoadhesive drug delivery system.…”

“…6 A mucoadhesive system loaded with an immune response modifier, imiquimod, for potential local treatment of precancerous oral lesions was previously developed. 7 Use of this delivery system would offer advantages of a non-invasive approach and reduced systemic effects of drugs.…”

“…7 Other properties relevant for developing a mucoadhesive system, however, were not investigated. The aim of the present studies was to characterize adhesion strength, swelling, tensile properties, and transport kinetics as a function of film composition and to subsequently investigate changes in drug release profiles.…”

Nanotechnology-based drug delivery systems for treatment of oral cancer: a review

“…199 Ramineni et al studied cyclodextrins for the inclusion of imiquimod to treat precancerous dysplastic lesions of the oral cavity. 200 This group developed a mucoadhesive film for the conveyance of a highly hydrophobic drug. To prepare these films, a polymer aqueous solution of polyvinylpyrrolidone mixed with ethanol following the addition of propylene …”

Advanced Drug Delivery Systems for Local Treatment of the Oral Cavity

“…Several other researchers are exploring the use of mucoadhesive drug delivery systems for chemoprevention of oral cancer [87,88]. Cid et al [89] explored chitosan gels for buccal delivery of the highly lipophilic celecoxib, a COX-2 inhibitor, for oral cancer chemoprevention.…”