Two-level delivery systems based on CaCO3 cores for oral administration of therapeutic peptides

Abstract

Two-level systems for oral delivery of therapeutic peptides were developed; the carriers consist of CaCO₃ cores included into alginate granules. Such systems were first used for the delivery of low molecular weight drugs. It was shown that efficiency of encapsulation of peptides depends on their pI value, hydrophobicity, characteristics of the compounds used for doping CaCO₃ cores, their surface potential and the techniques employed for loading peptides into the first-level carriers. Doping CaCO₃ cores with dextran sulphate save their viability compared to the pristine CaCO₃ cores, but ensures delivery of the desired quantity of peptide when using a smaller amount of delivery systems. Introducing the inhibitor of peptidases leads to an increase in the concentration of peptide in rat blood after intragastric administration of the developed delivery systems. Scanning electron microscopy and energy-dispersive X-ray spectroscopy demonstrated the presence of fragments of destructed first-level carriers in blood and plasma of experimental animals.