Oral peptide delivery using nanoparticles composed of novel graft copolymers having hydrophobic backbone and hydrophilic branches

Abstract

Nanoparticles composed of new graft copolymers having a hydrophobic backbone and hydrophilic branches were prepared by the dispersion copolymerization of hydrophilic polyvinyl macromonomers with styrene in a polar solvent. The potential of these nanoparticles as carriers for oral peptide delivery, was investigated using salmon calcitonin (sCT) in rats. The rate of sCT incorporated in nanoparticles was high and was affected by the macromonomer structure. Anionic nanoparticles having poly(methacrylic acid) macromonomer chains on their surfaces showed the highest incorporating activity. When the mixture of sCT and nanoparticles was administered orally, the decrease in the blood ionized calcium concentration was greater than that after oral administration of sCT aqueous solution. This hypocalcemic effect was also affected by the macromonomer structure, and the absorption of sCT was enhanced most strongly by nanoparticles having poly( N-isopropylacrylamide) macromonomer chains. However, the calcium concentration changed less when the nanoparticle concentration was low. On the other hand, the hypocalcemic effect was independent of the nanoparticle size and molecular weight of the macromonomers. The absorption enhancement of sCT by the nanoparticles probably results from both bioadhesion to the gastrointestinal (GI) mucosa and the increase of the stability of sCT in the GI tract. These nanoparticles were demonstrated to be useful carriers for incorporating highly water-soluble peptides and for enhancing peptide absorption via the GI tract.