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

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 concentrationson 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. Rezumatn ultimii 50 de ani, au fost dezvoltate numeroase peptide terapeutice, ns doar 4% sunt administrate oral, dei aceasta este calea preferat de pacieni.Administrarea oral a peptidelor este dificil din cauza degradrii enzimatice i a permeabilitii gastrice sczute.Co-formularea cu poteniatori de permeaie (PP) ofer o strategie viabil pentru mbuntirea biodisponibilitii obinute prin administrarea oral.Acest studiu evalueaz eficacitatea i sigurana a 4 PPn 2 concentraii diferite -asupra permeabilitii calcitoninei de somon (sCT) pe liniile celulare Caco-2: S-nitrozo-N-acetil-DL-penicilamin (SNAP), taurodeoxicolat de sodiu (TDC), dimetil-palmitoil-amoniu-propansulfonat (PPS) i tetradecil maltozid (TDM).Dintre PP investigai, TDM 0,2 mg/mL a crescut semnificativ permeabilitatea sCT, cu 282% fa de control (p = 0,017), cu 240% fa de SNAP 0,002 mg/mL (p = 0,01) i cu 149% fa de TDC 0,1 mg/mL (p = 0,036).Toi PP au sczut semnificativ rezistena electric transepitelial (RET) a liniilor celulare fa de control, cu cele mai mari efecte observate n primele 15 minute.TDM 1 mg/mL a produs cea mai mare reducere a RET, urmat de PPS 0,2 mg/mL i TDC 0,25 mg/mL.Valorile RET au fost cele mai sczute la 60 de minute, cu o recuperare parial observat dup dou ore, sugernd un efect reversibil.Aceste rezultate ar putea coordona cercetrile viitoare privind selectarea PP pentru co-formularea cu sCT sau cu alte peptide similare.