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

Context: 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 110.5 nm, -26.2 mV, 85.7% and 16.5% respectively. PUE from RGD/PEG-PUE-SLN exhibited sustained drug release with a burst release during the initial 12 h and a followed sustained release. Pharmacokinetics results indicated that AUC increased from 52.93 (mu g/mL h) for free PUE to 176.5 (mu g/mL h) for RGD/PEG-PUE-SLN. Similarly, T-1/2 increased from 0.73 h for free PUE to 2.62 h 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. Conclusion: We conclude that RGD modified and PEGylated SLN are promising candidate delivery vehicles for cardioprotective drugs in treatment of myocardial infarction. (C) 2017 Elsevier Masson SAS. All rights reserved.