Drug Delivery Systems of Fusion Proteins for the Treatment of Ischemic Heart Disease

Abstract

We developed novel in situ gel depot drug delivery systems for the protein delivery, in which a physical in situ gel, not chemically cross-linked, was formed by adding two oppositely charged biomacromolecules and the resulting complex coacervates were furthermore co-formulated with a negative thermosensitive polysaccharide containing a salting-out salt. An optimized novel delivery system containing dual advantages of complex coacervation and temperature responsiveness demonstrated a potential for Hsp-PTD fusion protein delivery in terms of sustained release, less initial burst, and stability of proteins in vitro. The animal experiment using rat LAD ischemia/perfusion (I/R) model showed that both Hsp-PTD solutions administered systemically and Hsp-PTD loaded in situ gel were very effective in reducing infarct size caused by hypoxia insult and enhancing echo functionality. This opens the possibility of using Hsp-PTD fusion protein delivery systems as new anti-apoptotic therapeutics preventing or treating ischemic heart diseases.