RGD modified and PEGylated lipid nanoparticles loaded with puerarin: Formulation, characterization and protective effects on acute myocardial ischemia model

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Zhaoqiang Dong, Jing Guo, Xiaowei Xing, Xuguang Zhang, Yimeng Du, Qinghua Lu
ContextPuerarin 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.ObjectiveRGD 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.MethodsIn 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.ResultsThe 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, T1/2 increased 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.ConclusionWe conclude that RGD modified and PEGylated SLN are promising candidate delivery vehicles for cardioprotective drugs in treatment of myocardial infarction.



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