POLYISOBUTYLCYANOACRYLATE NANOPARTICLES AS SUSTAINED-RELEASE SYSTEM FOR CALCITONIN

The potential of nanoparticles of polyisobutylcyanoacrylate as sustain ed release for peptide was assessed using calcitonin as a model drug. Calcitonin-loaded nanoparticles were obtained following the addition o f the peptide before or after polymerization of isobutylcyanoacrylate (CT-NP and CT/NP, respectively). For both formulations, the percentage of binding of calcitonin to the nanoparticles was more than 95% and t he particles had an average size of 150 nm. In vitro studies indicate that the release of calcitonin from CT/NP in saline solution containin g esterases resulted from the bioerosion of the polymer. However the p eptide was not released from CT-NP in this medium. SDS-PAGE electropho resis and HPLC also showed that calcitonin is tightly bound to the nan oparticles in the CT-NP formulation, very likely by a covalent binding . After intravenous injection in rats, free calcitonin, CT/NP and CT-N P had the same hypocalcemic activity (at the same dose). Following a s ubcutaneous injection in rats, the two encapsulated forms of calcitoni n showed a more important and more prolonged hypocalcemic effect than free calcitonin. 1 h after injection, calcitonin level was lower after CT-NP injection than CT/NP or free calcitonin injection. However, cal citonin level was sustained for more than 24 h after CT-NP injection.