Evaluation of the Safety, Cell Migration, and Mucoadhesive Properties of a Mucoadhesive Polymer Blend in Human Oral Mucosa.

Abstract

The efficacy of active pharmaceutical ingredients (API) in compounded medications for oral mucosa greatly depends on the composition of the base. Here, we assessed the safety, facilitation of cell migration, and mucoadhesive properties of a newly developed mucoadhesive polymer blend (MPB) which contains pullulan, tamarindus indica polysaccharide, and sodium hyaluronate. No cell death was observed when human oral keratinocyte (HOK) and fibroblast (HOrF) cells were exposed to 1% MPB for 24h. Epithelial cells in a 3D buccal tissue model (EpiOral) were unaffected when exposed to 50% MPB for 20h whereas 1% Triton X-100 killed 93% cells after 4.5h. The expressions of cytokines IL1α and IL1β and cell proliferation markers PCNA, CYCLIN A, and CYCLIN D1 in EpiOral tissue did not increase suggesting that MPB is neither an irritant nor a mitogen. Markers of apoptosis such as cleavage of CASPASES 8/9, upregulation of pro-apoptosis NOXA protein, and downregulation of anti-apoptosis XIAP protein were observed in Triton X-100-treated cells but not in cells exposed to MPB. The migration of HOK and HOrF cells was stimulated by MPB, and the expression of E-CADHERIN in the EpiOral tissues was unaffected. Moreover, MPB showed stronger mucoadhesion on the human EpiOral tissue model compared with a reference product. We conclude that MPB can safely deliver API within the oral mucosa, facilitate cell migration, and may increase drug efficacy through its strong mucoadhesive property.