2024-12-18 作者：ws 来源：https://www.sciencedirect.com/science/article/abs/pii/S0753332216327949文献：
RGD modified and PEGylated lipid nanoparticles loaded with puerarin:Formulation, characterization and protective effects on acute myocardial ischemia model
文献链接：
https://www.sciencedirect.com/science/article/abs/pii/S0753332216327949作者：
Zhaoqiang Dong, Jing Guo, Xiaowei Xing, Xuguang Zhang, Yimeng Du, Qinghua Lu
相关产品：
DSPE-PEG2000-NHS （二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000-活性酯）
DSPE-PEG2000（二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000）
原文摘要：
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-PUESLN) 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/PEGPUE-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 (mg/mL h) for free PUE to 176.5 (mg/mL h) for RGD/PEG-PUE-SLN. Similarly, T1/2 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.
DSPE-PEG2000-NHS是一种多功能的生物活性分子。它主要由 DSPE（1,2 -二硬脂酰 - sn -甘油- 3 -磷酸乙醇胺）、PEG2000（聚乙二醇，分子量为2000）和 NHS（N -羟基琥珀酰亚胺）组成。DSPE 部分赋予分子疏水性和磷脂特性，能够与细胞膜等脂质结构相互作用。PEG2000是亲水性的聚合物链，起到增加水溶性、改善生物相容性和延长循环时间的作用。NHS 是一种活性酯基团，它能够与含有氨基的分子发生化学反应，形成稳定的酰胺键。在溶解性方面，由于PEG2000 的存在，它在水中具有一定的溶解性，同时在一些有机溶剂如甲醇、乙醇、氯仿-甲醇混合溶剂等中也能溶解。该文献基于DSPE - PEG2000 - NHS的性质，制备了脂质纳米粒，过程如下：
图：产品结构方案
RGD-PEG-DSPE的合成过程：
RGD-PEG-DSPE采用一步法合成，在三乙胺（TEA）存在下，RGD的氨基与活化的DSPEPEG2000-NHS偶联。RGD溶解在无水N，N-二甲基甲酰胺中。在搅拌条件下，加入相当于RGD的TEA和DSPE-PEG2000-NHS，并在室温下搅拌溶液过夜。通过对去离子水的透析，在室温下透析，去除未反应的RGD。最后，通过冷冻干燥法得到了RGD-PEG-DSPE。
RGD/PEG-PUE-SLN的合成过程：
RGD/PEG-PUE-SLN采用溶剂蒸发法配制，并进行了一些修改。葛根素、888 ATO、可注射大豆卵磷脂和RGD-PEG-DSPE在乙醇中溶解融化，形成脂质相。水相由波洛克斯胺在双蒸馏水中组成，保持在一定温度。脂相在搅拌下注入热水相中，直到除去有机溶剂。PEG-PUE-SLN的配方与RGD/PEG-Pue-SLN的配方相同，只是用RGD-PEG-DSPE代替了PEG-DSPE。PUE-SLN的配方与RGD/PEG-Pue-SLN的配方相同，不含RGD-PEG-DSPE。空白SLN的配方与“Pue-SLN的配方”相同。
图：不同配方下浓度与时间曲线
结论：
该文献基于DSPE-PEG2000-NHS成功制备了RGD/PEGPUE-SLN，基于一系列详尽且有益的药代动力学和体内分布研究结果，我们可以得出结论：通过RGD的特异性修饰和聚乙二醇化策略对SLN进行改造，能够保护药物传递载体，增强其稳定性和生物相容性。
