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对心肌梗死模型的保护作用：使用基质金属蛋白酶敏感肽修饰的聚乙二醇化脂质纳米粒递送五味子醇甲

Protective effects on myocardial infarction model: delivery of schisandrin B using matrix metalloproteinase-sensitive peptide-modified, PEGylated lipid nanoparticles.

作者信息

Shao Mingfeng, Yang Wenfang, Han Guangying

机构信息

Department of Cardiology, Linyi People's Hospital, Linyi, Shandong, People's Republic of China.

Department of Internal Medicine, Linyi Hot Spring Hospital of Shandong Coal Mine, Linyi, Shandong, People's Republic of China.

出版信息

Int J Nanomedicine. 2017 Sep 26;12:7121-7130. doi: 10.2147/IJN.S141549. eCollection 2017.

DOI:10.2147/IJN.S141549
PMID:29026305
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5627750/
Abstract

PURPOSE

Schisandrin B (Sch B) is clinically applied for the treatment of hepatitis and ischemic disease. However, its clinical efficacy is limited due to the poor solubility and low bioavailability. This study aimed to develop matrix metalloproteinase (MMP)-sensitive peptide-modified, polyethylene glycol (PEG)-modified (PEGylated) solid lipid nanoparticles (SLNs) for loading Sch B (MMP-Sch B SLNs), and to evaluate the therapeutic effect in the myocardial infarction model.

METHODS

PEG lipid and MMP-targeting peptide conjugate were synthesized. MMP-Sch B SLNs were prepared by solvent displacement technique. The physicochemical properties and pharmacokinetics of SLNs were investigated. In vivo effects on infarct size was evaluated in rats.

RESULTS

The successful synthesis of lipid-peptide conjugate was confirmed. MMP-Sch B SLNs had a particle size of 130 nm, a zeta potential of 18.3 mV, and a sustained-release behavior. Higher heart drug concentration and longer blood circulation times were achieved by Sch B loaded SLNs than the drug solution according to the pharmacokinetic and biodistribution results. The best therapeutic efficacy was exhibited by MMP-Sch B SLNs by reducing the infarction size to the greatest extent.

CONCLUSION

The modified SLNs may be a good choice for delivery of Sch B for the treatment of myocardial infarction.

摘要

目的

五味子乙素（Sch B）临床上用于治疗肝炎和缺血性疾病。然而，由于其溶解性差和生物利用度低，其临床疗效有限。本研究旨在开发基质金属蛋白酶（MMP）敏感肽修饰、聚乙二醇（PEG）修饰（聚乙二醇化）的固体脂质纳米粒（SLN）用于负载Sch B（MMP-Sch B SLN），并评估其在心肌梗死模型中的治疗效果。

方法

合成PEG脂质和MMP靶向肽偶联物。采用溶剂置换技术制备MMP-Sch B SLN。研究SLN的理化性质和药代动力学。在大鼠中评估其对梗死面积的体内影响。

结果

证实脂质-肽偶联物成功合成。MMP-Sch B SLN粒径为130 nm，zeta电位为18.3 mV，具有缓释行为。根据药代动力学和生物分布结果，负载Sch B的SLN比药物溶液具有更高的心脏药物浓度和更长的血液循环时间。MMP-Sch B SLN通过最大程度地减小梗死面积表现出最佳治疗效果。

结论

修饰后的SLN可能是用于递送Sch B治疗心肌梗死的良好选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/5fbfb83b9f0d/ijn-12-7121Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/a8fb5c8f3f80/ijn-12-7121Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/e6e032ec5db5/ijn-12-7121Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/9f6b9925abb7/ijn-12-7121Fig3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/670e1107a323/ijn-12-7121Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/6d9599383607/ijn-12-7121Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/f2e016a8172b/ijn-12-7121Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/5fbfb83b9f0d/ijn-12-7121Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/a8fb5c8f3f80/ijn-12-7121Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/e6e032ec5db5/ijn-12-7121Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/9f6b9925abb7/ijn-12-7121Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/dac5017c22c5/ijn-12-7121Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/670e1107a323/ijn-12-7121Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/6d9599383607/ijn-12-7121Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/f2e016a8172b/ijn-12-7121Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d45/5627750/5fbfb83b9f0d/ijn-12-7121Fig8.jpg

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