Prolonged hypocalcemic effect by pulmonary delivery of calcitonin loaded poly(methyl vinyl ether maleic acid) bioadhesive nanoparticles.

ABSTRACT

The purpose of the present study was to design a pulmonary controlled release system of salmon calcitonin (sCT). Therefore, poly(methyl vinyl ether maleic acid) [P(MVEMA)] nanoparticles were prepared by ionic cross-linking method using Fe(2+) and Zn(2+) ions. Physicochemical properties of nanoparticles were studied in vitro. The stability of sCT in the optimized nanoparticles was studied by electrophoretic gel method. Plasma calcium levels until 48 h were determined in rats as pulmonary-free sCT solution or nanoparticles (25 µg · kg(-1)), iv solution of sCT (5 µg · kg(-1)), and pulmonary blank nanoparticles. The drug remained stable during fabrication and tests on nanoparticles. The optimized nanoparticles showed proper physicochemical properties. Normalized reduction of plasma calcium levels was at least 2.76 times higher in pulmonary sCT nanoparticles compared to free solution. The duration of hypocalcemic effect of pulmonary sCT nanoparticles was 24 h, while it was just 1 h for the iv solution. There was not any significant difference between normalized blood calcium levels reduction in pulmonary drug solution and iv injection. Pharmacological activity of nanoparticles after pulmonary delivery was 65% of the iv route. Pulmonary delivery of P(MVEMA) nanoparticles of sCT enhanced and prolonged the hypocalcemic effect of the drug significantly.