Sustained release of a p38 inhibitor from non-inflammatory microspheres inhibits cardiac dysfunction.

Sy JC, Seshadri G, Yang SC, Brown M, Oh T, Dikalov S, Murthy N, Davis ME
Nat Mater. 2008 7 (11): 863-8

PMID: 18931671 · PMCID: PMC2705946 · DOI:10.1038/nmat2299

Cardiac dysfunction following acute myocardial infarction is a major cause of death in the world and there is a compelling need for new therapeutic strategies. In this report we demonstrate that a direct cardiac injection of drug-loaded microparticles, formulated from the polymer poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK), improves cardiac function following myocardial infarction. Drug-delivery vehicles have great potential to improve the treatment of cardiac dysfunction by sustaining high concentrations of therapeutics within the damaged myocardium. PCADK is unique among currently used polymers in drug delivery in that its hydrolysis generates neutral degradation products. We show here that PCADK causes minimal tissue inflammatory response, thus enabling PCADK for the treatment of inflammatory diseases, such as cardiac dysfunction. PCADK holds great promise for treating myocardial infarction and other inflammatory diseases given its neutral, biocompatible degradation products and its ability to deliver a wide range of therapeutics.

MeSH Terms (19)

Animals Cell Line Delayed-Action Preparations Imidazoles Macrophage Activation Male Mice Mice, Inbred C57BL Microspheres Myocardial Infarction p38 Mitogen-Activated Protein Kinases Phosphorylation Polymers Protein Kinase Inhibitors Pyrimidines Rats Rats, Sprague-Dawley Superoxides Tumor Necrosis Factor-alpha

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