Absorption enhancement of orally administered salmon calcitonin by polystyrene nanoparticles having poly(N-isopropylacrylamide) branches on their surfaces

Abstract

Polystyrene nanoparticles having poly(N-isopropylacrylamide) branches on their surfaces (PNIPAAm nanoparticles) were synthesized and various attempts were made in rats to increase the absorption enhancement of orally administered salmon calcitonin (sCT) by these nanoparticles. The hypocalcemic effect after oral administration of a mixture of sCT and PNIPAAm nanoparticles depended greatly on the administration schedule. When one half of a dose of the mixture was given orally 40 min after the other half, sCT-induced hypocalcemic effect was markedly enhanced by PNIPAAm nanoparticles and the area of the reduction of the blood ionized calcium concentration was about 3 times that after administration of a single full dose of the same mixture. However, there was no further enhancement of the pharmacological activity of sCT when the half-doses were administered 120 min apart, sCT absorption was also affected by the hydrophobicity of the PNIPAAm nanoparticles. The hydrophobic PNIPAAm nanoparticles dispersed in hydrochloric acid-sodium chloride solution of pH 1.2, increased in sCT-induced hypocalcemic effect considerably. When two half-doses of the mixture containing these hydrophobic nanoparticles were given orally 40 min apart, the hypocalcemic effect remained strong, even though the dose was reduced to less than half. These changes probably depended on the bioadhesion of PNIPAAm nanoparticles to the gastric mucosa. It was demonstrated that PNIPAAm nanoparticles are good drug carriers that substantially enhance sCT absorption via the gastrointestinal tract.