A bioresponsive material for the localized delivery of molecules that inhibit the activity of a proteinase that is detrimental during heart attacks is reported in a study published online this week in Nature Materials. This method, which subsequently inhibits proteinase activity, shows therapeutic efficacy in preclinical animal models of myocardial infarction - where high activity levels of the proteinase can increase damage to parts of the heart.
Many diseases are characterized by high matrix metalloproteinase (MMP) activity and hence MMP inhibition is one therapeutic route to treat them. Following the systemic administration of MMP inhibitors, however, the side-effects are such that the dose that can be given is limited. Jason Burdick and colleagues now report a polysaccharide-based hydrogel that releases MMP inhibitors in response to high levels of MMP activity and hence reduces MMP activity at the desired location. The inhibitor-loaded hydrogel is injected directly into the tissue and inhibitors are released from the hydrogel when crosslinks within it degrade in the presence of MMP. In in vivo studies in pigs, the inhibitor-loaded hydrogel reduces the adverse effects observed within the ventricles of the heart following myocardial infarction. The localized delivery of MMP inhibitors could lessen off-target effects and aid the promotion of the clinical application of MMP-inhibitor-based therapies.
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