Penetratin enhanced salmon calcitonin permeation 5.5-fold through buccal cell layers and an extraordinary 93.7-fold through porcine buccal tissue at 12.2 µM.
93.7-foldcalcitonin permeation enhancement through buccal tissue using cell-penetrating peptide Penetratin
What the researchers found
Penetratin enhanced the delivery of salmon calcitonin (sCT) through both TR146 buccal cell layers and porcine buccal tissues in a concentration-dependent manner.
FITC-labeled Penetratin showed rapid intracellular uptake at low concentrations (0-15 micromolar) with a more gradual increase above 15 micromolar. The uptake of sCT increased alongside Penetratin concentration.
At 12.2 micromolar, Penetratin enhanced sCT flux 5.5-fold through TR146 cell layers and 93.7-fold through porcine buccal tissue. The dramatically higher enhancement in actual tissue suggests Penetratin works particularly well in the multi-layered environment of real buccal mucosa.
Why it matters
Many peptide drugs must be injected because they cannot pass through the body's barriers. Buccal (cheek) delivery could replace painful injections with a simple mouth application. Penetratin's dramatic enhancement of calcitonin delivery through cheek tissue suggests it could make this a viable route for large peptide drugs.
A 94-fold improvement in tissue permeation is remarkable and could bring buccal peptide delivery closer to practical use.
The numbers in context
5.5-fold enhancement (TR146 cells); 93.7-fold enhancement (porcine tissue); 12.2 μM Penetratin
How the study worked
This was a laboratory study using TR146 human buccal cancer cell layers and ex vivo porcine buccal tissues. Researchers co-applied fluorescently labeled Penetratin and calcitonin at various concentrations and measured uptake by flow cytometry and confocal microscopy. Permeation through cell layers and tissue was measured in Franz diffusion cells.
Who was studied
TR146 buccal cell layers and porcine buccal tissue
What this study cannot tell us
This was an in vitro and ex vivo study. The porcine tissue results are promising but may not fully predict human buccal permeation. No in vivo testing was performed.
Long-term safety of repeated Penetratin application on buccal tissue was not evaluated.
How to read the evidence
Preliminary evidence from in vitro cell layers and ex vivo porcine tissue. No in vivo or human data.
When this study was published
Published in 2020. Buccal peptide delivery remains an active research area.
The bigger picture
Buccal drug delivery could replace painful injections for peptide drugs like calcitonin, insulin, and GLP-1 agonists. A 94-fold permeation enhancement is remarkable and could make buccal peptide delivery clinically viable for the first time.
Questions still open
- Is the 94-fold enhancement reproducible in human buccal tissue?
- Would repeated Penetratin application damage the buccal mucosa?
- Could this approach work for other peptide drugs like insulin?
Common questions
What is buccal drug delivery?
Why is a 94-fold enhancement significant?
Read the original research
In Vitro and Ex Vivo Evaluation of Penetratin as a Non-invasive Permeation Enhancer in the Penetration of Salmon Calcitonin through TR146 Buccal Cells and Porcine Buccal Tissues.
Pharmaceuticals (Basel, Switzerland), 13(11)
Citation
Keum, Taekwang; Noh, Gyubin; Seo, Jo-Eun; Bashyal, Santosh; Lee, Sangkil. (2020). In Vitro and Ex Vivo Evaluation of Penetratin as a Non-invasive Permeation Enhancer in the Penetration of Salmon Calcitonin through TR146 Buccal Cells and Porcine Buccal Tissues.. Pharmaceuticals (Basel, Switzerland), 13(11). https://doi.org/10.3390/ph13110408