Abstract
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.
Highlights
The biopharmaceuticals market has increased significantly with the development of biotechnology in the past decades, and researches on formulations and drug delivery via various administration routes are actively being conducted [1]
The concentration of Penetratin and FITC-Penetratin treated to cells ranged from 2.5–160 μM
Cellular uptake and permeation studies were conducted in the rage of 0–40 μM where both Penetratin and FITC-Penetratin did not induce cytotoxicity
Summary
The biopharmaceuticals market has increased significantly with the development of biotechnology in the past decades, and researches on formulations and drug delivery via various administration routes are actively being conducted [1]. Oral administration is often preferred, but the oral route is not suitable for protein drugs due to the hepatic first pass effect, hydrolysis in the gastrointestinal tract, and enzymatic degradation in the small intestine [2,3]. To overcome these hurdles, protein drugs are administered through subcutaneous or intramuscular routes, generally with multiple injections because of their short half-life [4]. Various physical techniques and chemical enhancers are used to enhance the permeability of these biopharmaceuticals across the buccal mucosa. There are limitations to the use of physical techniques, such as iontophoresis and sonication because of their inaccessibility at home and high cost, and chemical enhancers are toxic at high concentrations [14]
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