| Summary: | 碩士 === 國立成功大學 === 醫學工程研究所碩博士班 === 98 === Heart failure is the top one killer of human beings in developed countries. The predominant cause of heart failure is coronary artery disease, which upon occlusion of the artery, lead to myocardial infarction with substantial cardiomyocyte necrosis and apoptosis. Therefore, therapies which prevent cardiomyocyte apoptosis after ischemic injury may prevent the development of heart failure.
The insulin-like Growth Factor (IGF)-1 has been shown to exert cardioprotection effect in vitro and in vivo. However, due to the small size of IGF molecules, direct injection of IGF-1 into infracted myocardium has limited benefits due to a rapid removal by circulation. To improve the retention time and thus cardiac beneficial effects of IGF-1, we have developed IGF-1 conjugated poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles (PLGA-IGF-1 NPs). We used the “electrostatic forces” method to fabricate PLGA-IGF-1NPs for delivering biologically functional IGF-1. The PLGA-IGF-1 NP size was ~74 nm. We showed that addition of PLGA-IGF-1 NPs inhibited Doxorubicin-induced cardiomyocyte apoptosis through the activation of Akt phosphorylation in vitro. In vivo, intramyocardial injection of PLGA-IGF-1 NPs had longer retention of IGF-1 than the injection of IGF-1 alone, and the retention lasted up to 24 hours. Furthermore, injection of PLGA-IGF-1 NPs into the peri-infarct areas prevented cardiomyocyte death, reduced the infarct size, and improved cardiac functions. This technology has potential for translation into a clinical therapy for ischemic heart disease.
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