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.
Lee
Jangwook
J
Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea.
Tan
Cheau Yih
CY
Lee
Sang-Kyung
SK
Kim
Yong-Hee
YH
Lee
Kuen Yong
KY
D000464:Alginates / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000737:chemistry; D006678:HIV / Q000737:chemistry*; D055551:HSP27 Heat-Shock Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D006360:Heat-Shock Proteins; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage / Q000737:chemistry; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry*; D008863:Microspheres; D018832:Molecular Chaperones; D032386:Myoblasts, Cardiac / Q000166:cytology; D009203:Myocardial Infarction / Q000188:drug therapy*; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage* / Q000235:genetics
D000464:Alginates; D003692:Delayed-Action Preparations; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D006603:Hexuronic Acids; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020723:Glucuronic Acid