Controlled delivery of heat shock protein using an injectable microsphere/hydrogel combination system for the treatment of myocardial infarction

Myocardial infarction causes a high rate of morbidity and mortality worldwide, and heat shock proteins as molecular chaperones have been attractive targets for protecting cardiomyoblasts under environmental stimuli. In this study, in order to enhance the penetration of heat shock protein 27 (HSP27) across cell membranes, we fused HSP27 with transcriptional activator (TAT) derived from human immunodeficiency virus (HIV) as a protein transduction domain (PTD). We loaded the fusion protein (TAT-HSP27) into microsphere/hydrogel combination delivery systems to control the release behavior for prolonged time periods. We found that the release behavior of TAT-HSP27 was able to be controlled by varying the ratio of PLGA microspheres and alginate hydrogels. Indeed, the released fusion protein maintained its bioactivity and could recover the proliferation of cardiomyoblasts cultured under hypoxic conditions. This approach to controlling the release behavior of TAT-HSP27 using microsphere/hydrogel combination delivery systems may be useful for treating myocardial infarction in a minimally invasive manner. (C) 2009 Elsevier B.V. All rights reserved.