title: RGD modified and PEGylated lipid nanoparticles loaded with puerarin: Formulation, characterization and protective effects on acute myocardial ischemia model.
abstract: BACKGROUND
  Puerarin has been widely used as a therapeutic agent for the treatment of cardiovascular diseases. However, its rapid elimination half-life in plasma and poor water solubility limits its clinical efficacy.
  
  
  OBJECTIVE
  RGD modified and PEGylated solid lipid nanoparticles loaded with puerarin (RGD/PEG-PUE-SLN) were developed to improve bioavailability of PUE, to prolong retention time in vivo and to enhance its protective effect on acute myocardial ischemia model.
  
  
  METHODS
  In the present study, RGD-PEG-DSPE was synthesized. RGD/PEG-PUE-SLN were prepared by the solvent evaporation method with some modifications. The physicochemical properties of NPs were characterized, the pharmacokinetics, biodistribution, pharmacodynamic behavior of RGD/PEG-PUE-SLN were evaluated in acute MI rats.
  
  
  RESULTS
  The mean diameter, zeta potential, entrapment efficiency and drug loading capacity for RGD/PEG-PUE-SLN were observed as 110.5nm, -26.2mV, 85.7% and 16.5% respectively. PUE from RGD/PEG-PUE-SLN exhibited sustained drug release with a burst release during the initial 12h and a followed sustained release. Pharmacokinetics results indicated that AUC increased from 52.93 (μg/mLh) for free PUE to 176.5 (μg/mLh) for RGD/PEG-PUE-SLN. Similarly, T1/2increased from 0.73h for free PUE to 2.62h for RGD/PEG-PUE-SLN. RGD/PEG-PUE-SLN exhibited higher drug concentration in the heart and plasma compared with other PUE formulations. It can be clearly seen that the infarct size of RGD/PEG-PUE-SLN is the lowest among all the formulation.
  
  
  CONCLUSIONS
  We conclude that RGD modified and PEGylated SLN are promising candidate delivery vehicles for cardioprotective drugs in treatment of myocardial infarction.
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, Ji'nan, 250033, Shandong, PR China. Electronic address: zhaoqiangdongsdu@163.com.
authors.forename: Zhaoqiang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Radiology, The Second Hospital of Shandong University, Ji'nan, 250033, Shandong, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, Ji'nan, 250033, Shandong, PR China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xing
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, Ji'nan, 250033, Shandong, PR China.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, Ji'nan, 250033, Shandong, PR China.
authors.forename: Yimeng
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, Ji'nan, 250033, Shandong, PR China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000818:Animals; D001682:Biological Availability; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry; D006801:Humans; D007529:Isoflavones / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008055:Lipids / Q000737:chemistry*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D053758:Nanoparticles / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D020011:Protective Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D003692:Delayed-Action Preparations; D007529:Isoflavones; D008055:Lipids; D010456:Peptides, Cyclic; D010714:Phosphatidylethanolamines; D020011:Protective Agents; C507169:cyclic arginine-glycine-aspartic acid peptide; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; C033607:puerarin
keywords: Active targeting; Arginine-glycineasparagine; Myocardial infarction; Passive targeting; Poly(ethylene glycol); Puerarin