TETRADECYL MALTOSIDE AND DIMETHYL-PALMITOYL-AMMONIO-PROPANE-SULFONATE AS EFFECTIVE PERMEATION ENHANCERS FOR SALMON CALCITONIN AND PRAMLINTIDE: A COMPARATIVE IN VITRO STUDY ON CACO-2 CELL LINES

Therapeutic peptides are increasingly used to treat chronic diseases due to their efficacy and safety profiles.However, the benefits observed in clinical trials often don't translate to real-world settings largely due to poor patient adherence caused by inconvenient injectable administration.While oral administration is preferred by chronic patients, it poses significant challenges for peptides including poor gastric absorption, low pH instability and susceptibility to proteolytic degradation.Considering the structural similarities between salmon calcitonin (sCT) and pramlintide (Pram), this in vitro study evaluates the efficacy and safety of tetradecyl maltoside (TDM) and dimethyl-palmitoyl-ammonio-propane-sulfonate (PPS) for enhancing the permeability of sCT compared to Pram on Caco-2 cell lines.TDM 0.2 mg/mL significantly increased the 2-hour apparent permeability coefficient (Papp) for sCT by 22% relative to TDM 1 mg/mL, but the effect did not reach statistical significance versus PPS 0.1 mg/mL and PPS 0.2 mg/mL.Conversely, PPS 0.1 mg/mL was the most effective permeation enhancer (PE) for Pram, inducing a 517% relative increase in 2-hour Papp versus TDM 1 mg/mL (p = 0.00002), 149% versus TDM 0.2 mg/mL (p = 0.00018) and 207% versus PPS 0.2 mg/mL (p = 0.00008).Thus, PPS 0.1 mg/mL is the most suitable PE for both peptides.At the 2-hour mark, both TDM and PPS significantly lowered transepithelial electrical resistance (TEER) at all concentrations, showing no signs of recovery 6 hours post-exposure.This study highlights the effectiveness of PPS as a viable permeation enhancer for both sCT and Pram, while also emphasizing the efficacy of TDM as a permeation enhancer specifically for sCT. RezumatDatorit profilurilor de eficacitate i siguran, peptidele terapeutice sunt utilizate din ce n ce mai frecvent n tratamentul bolilor cronice.ns, adesea beneficiile observate n studiile clinice nu se regsesc n practica clinic, n mare parte din cauza aderenei sczute la tratament a pacienilor, determinat de administrarea injectabil.Dei preferat de pacieni, administrarea oral a peptidelor este limitat de absorbia redus, instabilitatea la pH acid i degradarea proteolitic.Avnd n vedere similaritile structurale dintre calcitonina de somon (sCT) i pramlintid (Pram), acest studiu in vitro evalueaz eficacitatea i sigurana tetradecil maltozidei (TDM) i a dimetil-palmitoil-amoniu-propansulfonatului (PPS) privind creterea permeabilitii sCT comparativ cu Pram, pe linii celulare Caco-2.TDM 0,2 mg/mL a crescut semnificativ permeabilitatea sCT la 2 ore cu 22% versus TDM 1 mg/mL, dar fr semnificaie statistic versus PPS 0,1 mg/mL i PPS 0,2 mg/mL.n contrast, PPS 0,1 mg/mL a fost cel mai eficace poteniator de permeaie (PP) pentru Pram, inducnd o cretere relativ a permeabilitii la 2 ore cu 517% fa de TDM 1 mg/mL (p = 0,00002), cu 149% fa de TDM 0,2 mg/mL (p = 0,00018) i cu 207% fa de PPS 0,2 mg/mL (p = 0,00008).Astfel, reiese c PPS C1 este PP optim pentru ambele peptide.La 2 ore dup expunere, att TDM ct i PPS (ambele concentraii) au redus semnificativ rezistena electric transepitelial (RET), fr recuperare la 6 ore dup expunere.Acest studiu evideniaz eficacitatea PPS ca PP viabil pentru att pentru sCT, ct i pentru Pram i ntrete totodat eficacitatea TDM ca PP, n special pentru sCT.