ABSORPTION ENHANCEMENT OF ORALLY-ADMINISTERED SALMON-CALCITONIN BY POLYSTYRENE NANOPARTICLES HAVING POLY(N-ISOPROPYLACRYLAMIDE) BRANCHES ONTHEIR SURFACES

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. Th e hypocalcemic effect after oral administration of a mixture of sCT an d PNIPAAm nanoparticles depended greatly on the administration schedul e. When one half of a dose of the mixture was given orally 40 min afte r the other half, sCT-induced hypocalcemic effect was markedly enhance d by PNIPAAm nanoparticles and the area of the reduction of the blood ionized calcium concentration was about 3 times that after administrat ion of a single full dose of the same mixture. However, there was no f urther enhancement of the pharmacological activity of sCT when the hal f-doses were administered 120 min apart. sCT absorption was also affec ted by the hydrophobicity of the PNIPAAm nanoparticles. The hydrophobi c PNIPAAm nanoparticles dispersed in hydrochloric acid-sodium chloride solution of pH 1.2, increased in sCT-induced hypocalcemic effect cons iderably. When two hall-doses of the mixture containing these hydropho bic nanoparticles were given orally 40 min apart, the hypocalcemic eff ect remained strong, even though the dose was reduced to less than hal f. These changes probably depended on the bioadhesion of PNIPAAm nanop articles to the gastric mucosa. It was demonstrated that PNIPAAm nanop articles are good drug carriers that substantially enhance sCT absorpt ion via the gastrointestinal tract. (C) 1997 Elsevier Science B.V.