Abstract
Ischemic heart disease has emerged as a leading cause of death worldwide. Conventional surgery-based therapy for this disease, especially myocardial infarction, requires additional pharmaceutical agents using heart's endogenous protective mechanism to suppress the progress and recurrence of the disease. Heat shock protein 27 (Hsp27) has been considered to be a potentially therapeutic protein for the treatment of ischemic heart disease due to its anti-apoptotic and protective effects on cardiomyocytes under stressful conditions. Despite the potency of Hsp27, low transduction efficiency, protein instability, and a short half-life in the body have limited its in vivo applications. Protein transduction domains (PTD) were recombinantly fused with Hsp27 to enhance transduction efficiency. Although the intracellular delivery of the PTD-Hsp27 fusion proteins was significantly enhanced compared with Hsp27, the instability and short half-life of the PTD-Hsp27 fusion proteins still need to be improved for in vivo applications. Injectable thermo-reversible gel system was developed and found to be effective in stabilizing and retarding the release of the PTD-Hsp27 fusion proteins both in vitro and in vivo. PTD-Hsp27-loaded thermo-reversible gels were locally administered to the heart muscle in a ligation/reperfused rat myocardial infarction model and the long-term therapeutic efficacy was observed by measuring the inhibition of apoptosis and the area of fibrosis.
Original language | English |
---|---|
Pages (from-to) | 181-189 |
Number of pages | 9 |
Journal | Journal of Controlled Release |
Volume | 144 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2010 Jun |
Bibliographical note
Funding Information:This work was partially supported by grants from the Korea Science and Engineering Foundation ( 2009K001598 ) and the World Class University Project ( R332008000100360 ) funded by the Ministry of Education, Science, and Technology in Korea.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science