Studies On Myocardium-Targeting Liposome

To resolve the problem that the majority of cardiovascular pharmaceuticals (especially for protein and polypeptide drug) can not achieve a required therapeutic effect because of the lack of drug specific affinity toward pathological site and short t_1/2 in vivo, we designed a new myocardium-targeting liposome to increase the biodistribution of drugs in myocardium, especially in ischemic myocardium. The myocardium-targeting liposomes were modified with a myocardium targeting ligand, and their targetability to myocardium/ cardiomyocyte in vitro and in vivo were studied. The project was supported by National Natural Science Foundation of China (30271548).The following parts are included in this paper:1 Synthesis of targeting ligand and study of its bioactivity. The novel 3- {4-[2-hydroxyl- (1-methyl ethylamine) propyl oxygen] phenyl} propionic acid cetylester(PAC) was synthesized, which had similar structure with esmolol (a selective β₁-adrenoreceptor blocker). Its bioactivity of recognizing and binding to the β₁-adrenorece -ptor on the cardiomyocyte membrane was proved .2 Preparation of myocardium-targeting liposomes modified with PAC (PAC-L). The modification of 10 % PAC did not affect the size of liposomes, but could increase the zeta potential of liposomes (from - 12.8±0.8 mv to15.6±1.1 mv). A high affinity of PAC-L to cardiomyocytes was observed. The stability and toxicity of PAC-L were satisfied.3 The study on cardiomyocyte-targetability of PAC-L and targeting mechanism in vitro. At different lipid concentration and incubating time, the cardiomyocyte uptake of PAC-L was significantly higher than that of Plain-L (P<0.001). The addition of esmolol (0.1 mmol/L) could significantly decrease the cardiomyocyte uptake of PAC-L (P<0.001). This result indicated that the binding site of PAC-L and cardiomyocyte was competed by esmolol. So we can presume that PAC-L had the abilities of recognizing and binding to the...