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用于治疗心肌梗死的心房利钠肽修饰油酸腺苷前药脂质纳米载体：体外和体内评价

Atrial natriuretic peptide modified oleate adenosine prodrug lipid nanocarriers for the treatment of myocardial infarction: in vitro and in vivo evaluation.

作者信息

Yu Jianjun, Li Wei, Yu Dongmei

机构信息

Department of Emergency, Shandong Jining No 1 People's Hospital, Jining 272011, Shandong, People's Republic of China.

Department of Outpatient, Shandong Jining No 1 People's Hospital, Jining 272011, Shandong, People's Republic of China.

出版信息

Drug Des Devel Ther. 2018 Jun 11;12:1697-1706. doi: 10.2147/DDDT.S166749. eCollection 2018.

DOI:10.2147/DDDT.S166749
PMID:29928113
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6001834/
Abstract

PURPOSE

Myocardial infarction is a major cause of mortality and heart failure worldwide. One of the most effective methods of this injury is direct delivery of cardioprotective drugs to ischemia-reperfusion (IR) myocardium. The aim of the present study was to fabricate an adenosine (Ade) prodrug-based, atrial natriuretic peptide (ANP)-modified nanosystem for the treatment of myocardial infarction.

MATERIALS AND METHODS

Oleate adenosine prodrug (Ade-OA) and ANP-distearoylphosphatidylethanolamine-polyethylene glycol were synthesized. ANP-modified Ade-loaded lipid nanocarriers (ANP Ade/LNCs) were then self-assembled by using solvent evaporation method. In vitro drug release in the presence of plasma was evaluated. In vivo inhibition effect on infarct size, tissue distribution, and pharmacokinetics were investigated in rats with ischemic myocardium after intravenous injection.

RESULTS

In vivo inhibition effect on infarct size, tissue distribution, and pharmacokinetics studies in acute myocardial infarction (AMI) rats showed that ANP Ade/LNCs exhibited better efficiency than non-modified Ade/LNCs and free Ade in all respects.

CONCLUSION

These results indicated that the ANP Ade/LNCs can be used as a promising system for the treatment of cardiovascular diseases.

摘要

目的

心肌梗死是全球范围内导致死亡和心力衰竭的主要原因。对这种损伤最有效的方法之一是将心脏保护药物直接输送到缺血再灌注（IR）心肌。本研究的目的是制备一种基于腺苷（Ade）前药、心房利钠肽（ANP）修饰的纳米系统用于治疗心肌梗死。

材料与方法

合成油酸腺苷前药（Ade-OA）和ANP-二硬脂酰磷脂酰乙醇胺-聚乙二醇。然后采用溶剂蒸发法自组装ANP修饰的载Ade脂质纳米载体（ANP Ade/LNCs）。评估其在血浆存在下的体外药物释放。在静脉注射后，对缺血心肌大鼠的梗死面积、组织分布和药代动力学进行体内抑制作用研究。

结果

对急性心肌梗死（AMI）大鼠的梗死面积、组织分布和药代动力学的体内抑制作用研究表明，ANP Ade/LNCs在各方面均表现出比未修饰的Ade/LNCs和游离Ade更好的效果。

结论

这些结果表明，ANP Ade/LNCs可作为一种有前景的心血管疾病治疗系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/fe19378e7199/dddt-12-1697Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/ba563dbcd643/dddt-12-1697Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/037120948656/dddt-12-1697Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/f6617567282d/dddt-12-1697Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/9f16202a9076/dddt-12-1697Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/506a3acff5ab/dddt-12-1697Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/bdddca3a0325/dddt-12-1697Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/df1cffd735c4/dddt-12-1697Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/f2866f03e786/dddt-12-1697Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/fe19378e7199/dddt-12-1697Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/ba563dbcd643/dddt-12-1697Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/037120948656/dddt-12-1697Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/f6617567282d/dddt-12-1697Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/9f16202a9076/dddt-12-1697Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/506a3acff5ab/dddt-12-1697Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/bdddca3a0325/dddt-12-1697Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/df1cffd735c4/dddt-12-1697Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/f2866f03e786/dddt-12-1697Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/6001834/fe19378e7199/dddt-12-1697Fig9.jpg

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