ORAL PEPTIDE DELIVERY USING NANOPARTICLES COMPOSED OF NOVEL GRAFT-COPOLYMERS HAVING HYDROPHOBIC BACKBONE AND HYDROPHILIC BRANCHES

Nanoparticles composed of new graft copolymers having a hydrophobic ba ckbone and hydrophilic branches were prepared by the dispersion copoly merization of hydrophilic polyvinyl macromonomers with styrene in a po lar solvent. The potential of these nanoparticles as carriers for oral peptide delivery, was investigated using salmon calcitonin (sCT) in r ats. The rate of sCT incorporated in nanoparticles was high and was af fected by the macromonomer structure. Anionic nanoparticles having pol y(methacrylic acid) macromonomer chains on their surfaces showed the h ighest incorporating activity. When the mixture of sCT and nanoparticl es was administered orally, the decrease in the blood ionized calcium concentration was greater than that after oral administration of sCT a queous solution. This hypocalcemic effect was also affected by the mac romonomer structure, and the absorption of sCT was enhanced most stron gly by nanoparticles having poly(N-isopropylacrylamide) macromonomer c hains. However, the calcium concentration changed less when the nanopa rticle concentration was low. On the other hand, the hypocalcemic effe ct was independent of the nanoparticle size and molecular weight of th e macromonomers. The absorption enhancement of sCT by the nanoparticle s 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 incorporati ng highly water-soluble peptides and for enhancing peptide absorption via the GI tract. (C) 1997 Elsevier Science B.V.