Design and development of an anti-cancer agent targeting film

Corresponding author: aviramavital@campus.technion.ac.il

Oral cancer is the sixth most prevalent cancer worldwide with survival rates of only 40–50% ^[1]. The current treatments involve chemotherapy administration or irradiation following by surgery. However, these approaches are aggressive, invasive and non-specific which cause undesired adverse effects. Administering anti-cancer agents in close proximity to the cancerous lesion has proven clinically effective when dealing with head and neck tumors. To date, no drug delivery system for the controlled administration of anti-cancer agents to the oral cavity exists in the clinic. We previously developed a novel oral mucoadhesive delivery system based on the combination of alginate paste and liposomes ^[2]. One of the main challenges of this delivery system is to control the directional release of the liposomes containing the anti-cancer agent. In this study we develop a hydrophobic PLGA (poly (lactic-co-glycolic acid)) film providing enhanced drug release towards the cancerous tongue tissue and characterize its efficiency and mechanical properties. The film fabrication method was optimized by evaluating different mold types, film diameters, PLGA solution volumes and concentrations. Tensile study presents film’s resistance to tensile forces and stiffness maintaining during 24 hours in an environment that simulates the oral cavity, indicating film stability. To assess film’s efficiency, permeation study was performed on different drug-model molecules that were encapsulated inside liposomes and incorporated into the polymeric matrix. Results indicate that the film is highly impermeable for the passage of both liposomal small molecule and protein as a result improving drug targeting towards the cancerous lesion. Thus, our PLGA film is adequate for controlling the directional release of oral mucoadhesive delivery system.

References:
[1] Howlader, N., et al. "SEER Cancer Statistics Review, 1975–2014, SEER Cancer Statistics Review." (2016).

[2] Shtenberg, Yarden, et al. "Mucoadhesive alginate pastes with embedded liposomes for local oral drug delivery." International journal of biological macromolecules 111 (2018): 62-69.