Mucoadhesive Patches for Intraoral Delivery of Immune Response Modifiers

Objective: Imiquimod amplifies immune response in virally infected, neoplastic, and dysplastic cells. Its use in the oral cavity has been limited in part due to issues of drug delivery. Because of the moist environment of the oral cavity, the application of imiquimod to the mucosa presents several challenges, including adhesion to tissue, dose consistency, and residence time. The goal of the present study was to develop a mucoadhesive patch made from FDA-approved materials for the intraoral delivery of imiquimod at predicable doses and for appropriate duration. Methods: Film-forming polymer polyvinylpyrrolidone (PVP) and mucoadhesive polymer carboxymethylcellulose (CMC) were selected for use based on previous studies. Separately made PVP (with ethanol and propylene glycol) and CMC solutions (with imiquimod) were mixed in testing ratios (v/v) of 1:2 and 2:1, then cast in Teflon dishes, and desiccated to form delivery matrices. Mass loss studies were used to assess in vitro bioerosion and potential residence time of the films. Drug release was evaluated through fluorescence analysis on aliquots of the supernatant from imiquimod-loaded samples. Results: In vitro degradation studies revealed two distinct profiles for the two compositions tested. Dissolution of the mucoadhesive patches in simulated saliva solution showed average total matrix erosion times of 180 min. and 400 min. for 2:1 and 1:2 PVP:CMC, respectively. Drug-release reflected the erosion of the polymers. The faster-degrading 2:1 PVP:CMC initially released larger doses of imiquimod, but they decreased with time. In contrast, the more slowly eroding 1:2 PVP:CMC released smaller doses at the beginning, but amounts increased until the materials were gone. Conclusion: The mucoadhesive patches' adhesion, dissolution, and drug release characteristics, coupled with the ability to vary residence time through a range of polymer ratios, demonstrate its promise as a vehicle for intraoral transmucosal delivery of immune response modifiers, such as imiquimod.