Abstract 1135: Drug Delivery System Targeting the Injured Myocardium
Background: Drug delivery system (DDS) targeting the injured myocardium has a great potential as a novel therapeutic approach for myocardial infarction; however, an efficient method of injured myocardium-targeted DDS has not been established. To develop DDS targeting the injured myocardium, we focused on a glycoside-binding protein (GBP) expressed in myocytes and hypothesized that the interaction between GBP and glycosides-conjugated agents can utilize DDS. In the present study, we screened GBP expression in cardiomyocytes and tried the developed a novel DDS targeting the injured myocardium.
Methods and Results: To search the GBP of cardiomyocytes, we first screened the GBP by various glycoside-binding assay and found that rat cardiomyocytes had the GBP that recognizes N-acetylglucosamine (GlcNAc). To investigate whether this GBP could be utilized as DDS for the injured myocardium, the GlcNAc-conjugated FITC-polystyrene nano-particles (200 nm) were prepared. The specific delivery of these nano-particles to the injured myocardium was analyzed in a mouse model of myocardial ischemia-reperfusion in vivo. After the nano-particles were injected into these models intravenously, the nano-particles markedly accumulated in the area of injured myocardium. Next, to deliver the therapeutic agents to cardiomyocytes, we prepared GlcNAc-conjugated liposomes (GlcNAc-Ls) containing a fluorescent substrate or a hydrophilic statin pravastatin which is difficult to incorporate into the cells. Flow cytometry analysis showed that GlcNAc-Ls containing a fluorescent substrate bound to and was incorporated into cardiomyocytes in vitro. Further, the production of nitric oxide in interleukin-1β-stimulated cardiomyocytes was enhanced by incorporation of GlcNAc-Ls containing pravastatin, but not the treatment of the unmodified pravastatin.
Conclusions: This novel DDS approach using cardiomyocyte-expressing GBP is a promising potential for the treatment of myocardium ischemia-reperfusion injury.