Buccal drug delivery is a suitable alternative to invasive routes of drug administration. The buccal administration of insulin for the management of diabetes has received substantial attention worldwide. The main aim of this study was to develop and characterize elastic liposomes and assess their permeability across porcine buccal tissues. Sodium-cholate-incorporated elastic liposomes (SC-EL) and sodium-glycodeoxycholate-incorporated elastic liposomes (SGDC-EL) were prepared using the thin-film hydration method. The prepared liposomes were characterized and their ex vivo permeability attributes were investigated. The distribution of the SC-EL and SGDC-EL across porcine buccal tissues was evaluated using confocal laser scanning microscopy (CLSM). The SGDC-EL were the most superior nanocarriers since they significantly enhanced the permeation of insulin across porcine buccal tissues, displaying a 4.33-fold increase in the permeability coefficient compared with the insulin solution. Compared with the SC-EL, the SGDC-EL were better at facilitating insulin permeability, with a 3.70-fold increase in the permeability coefficient across porcine buccal tissue. These findings were further corroborated based on bioimaging analysis using CLSM. SGDC-ELs showed the greatest fluorescence intensity in buccal tissues, as evidenced by the greater shift of fluorescence intensity toward the inner buccal tissue over time. The fluorescence intensity ranked as follows: SGDC-EL > SC-EL > FITC–insulin solution. Conclusively, this study highlighted the potential nanocarriers for enhancing the buccal permeability of insulin.

Buccal tissues are considered one of the potential alternative delivery route because of fast drug absorption and onset of action due to high vascularization and a non-keratinized epithelial membrane. In this study, the effect of Penetratin on the permeation of salmon calcitonin (sCT), a model macromolecular peptide drug, through TR146 buccal cells and porcine buccal tissues has been evaluated. To observe permeation profile of sCT, TR146 buccal cells were treated with Alexa 647 conjugated sCT (Alexa 647-sCT) with different concentrations of fluorescein isothiocyanate -labeled Penetratin (FITC-Penetratin) ranging from 0 to 40 μM, and analyzed using flow cytometry and confocal laser scanning microscopy. Intracellular penetration of FITC-Penetratin rapidly increased at low concentrations from 0 to 15 μM and it gradually increased at concentrations above 15 μM. Intracellular penetration of Alexa 647-sCT enhanced with the increase of FITC-Penetratin concentration. When TR146 cell layers and buccal tissues were co-treated with sCT and Penetratin as permeation enhancer, the flux of sCT increased as per Penetratin concentration. Compared to the control, 12.2 μM of Penetratin enhanced the flux of sCT in TR146 cell layers and buccal tissues by 5.5-fold and 93.7-fold, respectively. These results strongly suggest that Penetratin may successfully act as a non-invasive permeation enhancer for macromolecular peptide drug delivery through buccal routes.