Preparation, in vitro and in vivo evaluation of chitosan-sodium alginate-ethyl cellulose polyelectrolyte film as a novel buccal mucosal delivery vehicle

•Chitosan-sodium alginate-ethyl cellulose (CS-SA-EC) film was developed by solvent-spray drying technique.•The CS-SA-EC films had mechanical and bioadhesive properties, and the effect of controlled release.•The changes in molecular weight and deacetylation degree of CS would affect the properties of the film.•The enhancement of the drugs permeability by the CS-SA-EC films may be related to the regulation of the ZO-1 protein.•The bioavailability of drugs was significantly improved by the CS-SA-EC films. This paper describes the development of a film comprising chitosan (CS), sodium alginate (SA), and ethyl cellulose (EC) for buccal mucosal administration. A film of CS-SA unidirectional release drug-containing water-repellent layer EC was produced by interfacial reaction solvent-drying technique using self-made equipment. The CS-SA-EC film had superior mechanical properties compared to CS-EC and SA-EC films. The existence of the amide bond was confirmed by FT-IR. DSC confirmed that the drug was dispersed in the carrier material in an amorphous form. The drug release studies emerged that the model drugs from CS-SA-EC films presented better release properties. The Ritger-Peppas model best describes all ratios of drugs release mechanisms. The permeability characteristics of the films were evaluated in the TR146 cells model and the rabbit buccal mucosae. The cumulative penetration amounts of the model drugs were significantly increased. The permeability mechanism of the film was studied preliminarily using immunofluorescence and Western Blot. The results showed that the film inhibited the expression of ZO-1 protein, and the expressive trend of ZO-1 protein was consistent with the results of in vitro permeation experiments. The pharmacokinetics of the drugs loaded films were evaluated and compared with oral administration in rats. The relative bioavailability of the model drugs was 246.00% (Zolmitriptan) and 142.12% (Etodolac) relative to oral administration. The results of this study demonstrate the potential of CS-SA-EC vehicle in buccal mucosa drug delivery. Graphical abstract [Display omitted]