Cell-Penetrating Peptide Penetratin Boosts Calcitonin Delivery Through Cheek Tissue 94-Fold

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.

Keum, Taekwang et al.·Pharmaceuticals (Basel·2020·Preliminary Evidencein vitro
RPEP-04903In vitroPreliminary Evidence2020RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
in vitro
Evidence
Preliminary Evidence
Sample
N=N/A (in vitro/ex vivo)
Participants
TR146 buccal cell layers and porcine buccal tissue

What This Study 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.

Key Numbers

5.5-fold enhancement (TR146 cells); 93.7-fold enhancement (porcine tissue); 12.2 μM Penetratin

How They Did This

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.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

  • ?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?

Trust & Context

Key Stat:
93.7-fold calcitonin permeation enhancement through buccal tissue using cell-penetrating peptide Penetratin
Evidence Grade:
Preliminary evidence from in vitro cell layers and ex vivo porcine tissue. No in vivo or human data.
Study Age:
Published in 2020. Buccal peptide delivery remains an active research area.
Original Title:
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.
Published In:
Pharmaceuticals (Basel, Switzerland), 13(11) (2020)
Database ID:
RPEP-04903

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

What is buccal drug delivery?

Applying medication to the inside of the cheek, where it absorbs through the tissue into the bloodstream. This bypasses the stomach (which destroys peptides) and avoids needles.

Why is a 94-fold enhancement significant?

Most peptide drugs cannot cross buccal tissue at all — the absorption is near zero. A 94-fold increase brings the amount that crosses into a range that could be therapeutically useful.

Read More on RethinkPeptides

Cite This Study

RPEP-04903·https://rethinkpeptides.com/research/RPEP-04903

APA

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

MLA

Keum, Taekwang, et al. "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, 2020. https://doi.org/10.3390/ph13110408

RethinkPeptides

RethinkPeptides Research Database. "In Vitro and Ex Vivo Evaluation of Penetratin as a Non-invas..." RPEP-04903. Retrieved from https://rethinkpeptides.com/research/keum-2020-in-vitro-and-ex

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.