BIODEGRADABLE NANOPARTICLES FOR SUBCUTANEOUS ADMINISTRATION OF GROWTH-HORMONE RELEASING-FACTOR (HGRF)

This paper shows that biodegradable Poly Iso Hexyl Cyanoacrylate (PIHCA) nanoparticles are able to deliver Growth Hormone Releasing Factor (GRF) as a sustained-release system. Using nanoparticles, GRF plasma levels may be maintained constant for at least 24 h after the injection, after which GRF is still significantly present in the plasma, whereas, with free GRF, the maximum plasma concentration appears 2 min after the administration and no GRF can be detected after 100 min. The fact that nanoparticles are able to deliver sustained-release GRF after subcutaneous administration is consistent with the in vivo behaviour of radiolabelled nanoparticles as shown by autoradiography. In these experiments, nanoparticles are found to remain at the injection site for at least 24 h after subcutaneous administration. This was confirmed by transmission electron microscopy studies, which showed undegraded nanoparticles at the injection site after 24 h. Moreover, nanoparticles are able to protect GRF against enzymatic degradation. Analyses of the injection site 24 hours after subcutaneous administration have shown undegraded GRF in the nanoparticles. This fact could explain why GRF bioavailability was improved when administered in a nanoparticle formulation.