Optimization of Mucoadhesive Oral Films Containing Olive Leaf Extract and Microencapsulated Thyme Essential Oil With...

In this study, developing mucoadhesive oral films with optimized olive leaf extract (OLE) and microencapsulated thyme essential oil (TEO) contents was aimed to create a novel oral delivery system with desirable film properties as well as enhanced bioactivities. For this, TEO-containing sodium alginate/okra gum microcapsules were first fabricated at optimized electrospray conditions, where optimization was performed for three parameters, which are the flow rate of the emulsion solution, the potential difference, and the distance between the nozzle of the sample container and the collector plate, through three-level centered Box-Behnken design. Prior to the inclusion of the OLE in custom-designed mucoadhesive films, polymeric components of the films were also optimized through a separate multi-variable, three-level Box-Behnken experimental design by which the effect of mixing ratios of Carbopol 934, hydroxypropyl methylcellulose and polyethylene glycol on viscosity, solution pH, film pH, disintegration time, thickness, and weight were elaboratively investigated. The resulting films, containing OLE and microencapsulated TEO, obtained through solvent casting were characterized for pH, viscosity, mass uniformity and thickness, dispersion, tensile strength, folding endurance, contact angle, in vitro mucoadhesion time, and ex vivo mucoadhesion force. Results showed that the film had good tensile strength, swelling capacity, compatibility with oral mucosa, and flexibility. It also demonstrated desirable stability and adhesion ability. Regarding bioactivity, the film was found to have desirable antioxidant capacity and it was non-toxic to fibroblast cells when diluted to certain concentration. Moreover, antiviral studies indicated reductions of 32.39% and 54.29% against Poliovirus Type 1 and Murine Norovirus, respectively, while preliminary antibacterial tests showed no significant reduction in certain bacteria within 1 min, but a logarithmic reduction in Staphylococcus aureus was observed. Despite favorable mucoadhesion properties and physical attributes, further investigation is needed to enhance the antimicrobial effectiveness of the films for their potential utilization in drug delivery systems.