title: Injectable microsphere/hydrogel hybrid system containing heat shock protein as therapy in a murine myocardial infarction model.
abstract: Heat shock proteins, acting as molecular chaperones, protect heart muscle from ischemic injury and offer a potential approach to therapy. Here we describe preparation of an injectable form of heat shock protein 27, fused with a protein transduction domain (TAT-HSP27) and contained in a hybrid system of poly(d,l-lactic-co-glycolic acid) microsphere and alginate hydrogel. By varying the porous structure of the microspheres, the release of TAT-HSP27 from the hybrid system was sustained for two weeks in vitro. The hybrid system containing TAT-HSP27 was intramyocardially injected into a murine myocardial infarction model, and its therapeutic effect was evaluated in vivo. The sustained delivery of TAT-HSP27 substantially suppressed apoptosis in the infarcted site, and improved the ejection fraction, end-systolic volume and maximum pressure development in the heart. Local and sustained delivery of anti-apoptotic proteins such as HSP27 using a hybrid system may present a promising approach to the treatment of ischemic diseases.
authors: Department of Bioengineering, Hanyang University , Seoul , Republic of Korea .
authors: Jangwook
authors: J
authors: Lee
authors: Min-Ji
authors: MJ
authors: Cha
authors: Kwang Suk
authors: KS
authors: Lim
authors: Jang-Kyung
authors: JK
authors: Kim
authors: Sang-Kyung
authors: SK
authors: Lee
authors: Yong-Hee
authors: YH
authors: Kim
authors: Ki-Chul
authors: KC
authors: Hwang
authors: Kuen Yong
authors: KY
authors: Lee
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D015696:Gene Products, tat / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020723:Glucuronic Acid / Q000737:chemistry; D055551:HSP27 Heat-Shock Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006603:Hexuronic Acids / Q000737:chemistry; D020100:Hydrogels; D020287:In Situ Nick-End Labeling; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008863:Microspheres; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000464:Alginates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D015696:Gene Products, tat; D055551:HSP27 Heat-Shock Proteins; D006603:Hexuronic Acids; D020100:Hydrogels; D011993:Recombinant Fusion Proteins; C582517:TAT-HSP27 fusion protein, human; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020723:Glucuronic Acid