(647d) Engineering of Degradable Biopolymer Films Loaded with Imiquimod for Controlled Released in a Mucosal Environment

Oral cancer is one of the most common neoplasia, with over 450 thousand new cases worldwide being diagnosed each year. In the United States only, it is estimated that a total of approximately $3.2 billion is spent yearly on treatment of head and neck cancers. One of the most common procedures for this type of cancer is the surgical resection of the lesioned tissue, usually when the disease has already evolved to oral squamous cell carcinoma (OSCC), which may affect mouth and throat lining cells. A major drawback of this aggressive approach is the postoperative functional and esthetic sequelae that can result from the procedures, such as the loss of the ability to swallow due to the impairment of essential tissues. Given these potential problems associated with surgical resection, in this study we aimed to develop a degradable mucoadhesive film, composed of the biopolymers chitosan (C) and alginate (A), loaded with the antineoplastic agent imiquimod (IM).

Both C and A are mucoadhesive polymers, being capable to interact with the glycoproteins of the buccal mucosa. Through buccal adhesion it is possible to tailor drug delivery to oral lesions in situ, both improving and prolonging the contact of the bioactive agent with the tumor, increasing drug bioavailability and uptake. The drug utilized in this system, IM, is a Toll-like receptor 7 (TLR7) agonist that up-regulates cytokines and generates an immune response. This compound is extensively used in the treatment of skin neoplasms, but reports on its effects upon the proliferation of OSCC are still scarce. Focusing on optimizing the controlled release of the drug, several formulations of the films were analyzed, both based on the isolated biopolymers or involving their combination in different proportions. The films were characterized with respect to morphology, infrared spectra, thickness, mucoadhesion, stability in physiological solutions, thermal stability, mechanical properties, drug incorporation efficiency, IM release kinetics and antitumor potential in OSCC.

The drug was efficiently loaded into thin films (incorporation efficiencies above 60% in films with average thickness below 0.14 mm). IM was distributed in the polysaccharide matrix as amorphous aggregates or as rods, depending on the conditions of film production. In general, IM incorporation reduced the tensile strength of the films, but did not alter their mucoadhesion properties. For most formulations developed, efficient release of the drug was noticed in less than 8 hours, as a result of film swelling and degradation after exposure to simulated saliva, suggesting promising results in vivo.

The authors are grateful for the financial support of this work by the Brazilian National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Education Personnel (CAPES), and by the São Paulo Research Foundation (FAPESP), all from Brazil.