ARTICLE AUTHOR: Tasset-C; Barette-N; Thysman-S; Ketelslegers-JM; Lemoine-D; Preat-V

REPRINT AUTHOR: Preat, V; UNIV CATHOLIQUE LOUVAIN; UNITE PHARM GALEN, AVE E MOUNIER 7320; B-1200 BRUSSELS; BELGIUM

SOURCE: JOURNAL-OF-CONTROLLED-RELEASE. JAN 1995; 33 (1) : 23-30

ABSTRACT:

The potential of nanoparticles of polyisobutylcyanoacrylate as sustained release for peptide was assessed using calcitonin as a model drug. Calcitonin-loaded nanoparticles were obtained following the addition of 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 the particles had an average size of 150 nm. In vitro studies indicate that the release of calcitonin from CT/NP in saline solution containing esterases resulted from the bioerosion of the polymer. However the peptide was not released from CT-NP in this medium. SDS-PAGE electrophoresis and HPLC also showed that calcitonin is tightly bound to the nanoparticles in the CT-NP formulation, very likely by a covalent binding. After intravenous injection in rats, free calcitonin, CT/NP and CT-NP had the same hypocalcemic activity (at the same dose). Following a subcutaneous injection in rats, the two encapsulated forms of calcitonin 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, calcitonin level was sustained for more than 24 h after CT-NP injection.