Romanian Society of Pharmaceutical Sciences

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A COMPARATIVE STUDY OF FOUR PERMEATION ENHANCERS FOR INCREASING THE TRANSPORT OF SALMON CALCITONIN ON CACO-2 CELL LINES

ANDREI HAMZA 1*, GABRIEL ȘARAMET 1

1 “Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmacy, 37 Dionisie Lupu Street, Bucharest, 020021, Romania

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Over the past 50 years, research has led to the development of effective peptide-based macromolecules, yet only 4% are administered orally, despite patient preference. Oral delivery of peptides is challenging due to degradation by proteolytic enzymes and low gastric permeability. Co-formulation with permeation enhancers (PEs) offers a promising strategy to overcome these barriers and improve oral bioavailability. This study evaluates the efficacy and safety of 4 PEs - in 2 different concentrations - on the permeability of salmon calcitonin (sCT) in Caco-2 cell lines: S-nitroso-N-acetyl-DL-penicillamine (SNAP), sodium taurodeoxycholate (TDC), dimethyl-palmitoyl-ammonio-propane-sulfonate (PPS) and tetradecyl maltoside (TDM). Among the PEs tested, TDM 0.2 mg/mL significantly increased sCT permeability, with a 282% increase versus control (p = 0.017), 240% versus SNAP 0.002 mg/mL (p = 0.01) and 149% versus TDC 0.1 mg/mL (p = 0.036). All PEs significantly decreased the transepithelial electrical resistance (TEER) of the cell lines versus control, with the strongest effects observed within the first 15 minutes. TDM 1 mg/mL caused the most significant TEER reduction, followed by PPS 0.2 mg/mL and TDC 0.25 mg/mL. TEER values were lowest at 60 minutes, with partial recovery noted at two hours, suggesting potential reversibility. These findings could guide future research in selecting the optimal PE for co-formulation with sCT or other peptides with similar molecular characteristics.