Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alginates / administration & dosage
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Alginates / chemistry
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Apoptosis / drug effects
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Cell Hypoxia / drug effects
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Cell Line
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Delayed-Action Preparations / administration & dosage
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Delayed-Action Preparations / pharmacology
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Delayed-Action Preparations / therapeutic use
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Glucuronic Acid / administration & dosage
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Glucuronic Acid / chemistry
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HIV / chemistry*
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HSP27 Heat-Shock Proteins / administration & dosage*
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HSP27 Heat-Shock Proteins / genetics
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HSP27 Heat-Shock Proteins / pharmacology*
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HSP27 Heat-Shock Proteins / therapeutic use
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Heat-Shock Proteins
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Hexuronic Acids / administration & dosage
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Hexuronic Acids / chemistry
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Humans
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Hydrogel, Polyethylene Glycol Dimethacrylate / administration & dosage
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Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
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Lactic Acid / administration & dosage
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Lactic Acid / chemistry*
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Microspheres
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Molecular Chaperones
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Myoblasts, Cardiac / cytology
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Myocardial Infarction / drug therapy*
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Polyglycolic Acid / administration & dosage
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Polyglycolic Acid / chemistry*
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Polylactic Acid-Polyglycolic Acid Copolymer
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / pharmacology
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Recombinant Fusion Proteins / therapeutic use
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tat Gene Products, Human Immunodeficiency Virus / administration & dosage*
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tat Gene Products, Human Immunodeficiency Virus / genetics
Substances
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Alginates
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Delayed-Action Preparations
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HSP27 Heat-Shock Proteins
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HSPB1 protein, human
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Heat-Shock Proteins
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Hexuronic Acids
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Molecular Chaperones
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Recombinant Fusion Proteins
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tat Gene Products, Human Immunodeficiency Virus
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Polylactic Acid-Polyglycolic Acid Copolymer
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Hydrogel, Polyethylene Glycol Dimethacrylate
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Polyglycolic Acid
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Lactic Acid
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Glucuronic Acid