Development of imiquimod-loaded mucoadhesive films for oral dysplasia

Sandeep K. Ramineni, Larry L. Cunningham, Thomas D. Dziubla, David A. Puleo

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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 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-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 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.

Original languageEnglish
Pages (from-to)593-603
Number of pages11
JournalJournal of Pharmaceutical Sciences
Volume102
Issue number2
DOIs
StatePublished - Feb 2013

Bibliographical note

Funding Information:
This work was supported in part by the National Institutes of Health (DE019645) and Kentucky NASA EPSCoR (NNX08BA13A). The authors thank Dr. Heidi Mansour (University of Kentucky College of Pharmacy) for assistance with DSC measurements and gratefully recognize the contributions of Mr. J.D. Christensen and Ms. Laynie Boland toward early development of the films.

Keywords

  • 2-hydroxypropyl-β-cyclodextrin
  • Biomaterials
  • Carboxymethylcellulose
  • Controlled release/delivery
  • Mucosal drug delivery
  • Oral cancer
  • Polymeric drug carrier
  • Polyvinylpyrrolidone
  • Solubility

ASJC Scopus subject areas

  • Pharmaceutical Science

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