Guangzhou First People's Hospital, School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 510006, P.R. China.
School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P.R. China.
ACS Nano. 2020 Mar 24;14(3):3563-3575. doi: 10.1021/acsnano.9b10015. Epub 2020 Feb 19.
Polymeric nanoparticles (NPs) are an important category of drug delivery systems, and their fate is closely associated with delivery efficacy. Analysis of the protein corona on the surface of NPs to understand the fate of different NPs has been shown to be reliable but complicated and time-consuming. In this work, we establish a simple approach for predicting the fate of polymeric NPs. We prepared a series of poly(ethylene glycol)--poly(d,l-lactide) (PEG--PLA) NPs with different protein binding behaviors by adjusting their PEG densities, which were determined by analyzing the serum protein adsorption. We further determined the protein binding affinity, denoted as the equilibrium association constant (), to correlate with fate of NPs. The fate, including blood clearance and Kupffer cell uptake, was studied, and the maximum concentration (), the area under the plasma concentration-time curve (AUC), and the mean residence time (MRT) were negatively linearly dependent, while Kupffer cell uptake was positively linearly dependent on . Subsequently, we verified the reliability of the approach for fate prediction using poly(methoxyethyl ethylene phosphate)--poly(d,l-lactide) (PEEP--PLA) and poly(vinylpyrrolidone)--poly(d,l-lactide) (PVP--PLA) NPs, and the linear relationship between the value and their PK parameters further suggests that the protein binding affinity of polymeric NPs can be a direct indicator of their pharmacokinetics.
聚合物纳米粒子（NPs）是一种重要的药物传递系统类别，其命运与传递效率密切相关。分析 NPs 表面的蛋白质冠来了解不同 NPs 的命运已被证明是可靠的，但复杂且耗时。在这项工作中，我们建立了一种预测聚合物 NPs 命运的简单方法。我们通过调整其聚乙二醇（PEG）密度来制备一系列具有不同蛋白质结合行为的聚（乙二醇）-聚（dl-丙交酯）（PEG-PLA）NPs，PEG 密度通过分析血清蛋白吸附来确定。我们进一步确定了蛋白质结合亲和力，用平衡缔合常数（）表示，与 NPs 的命运相关联。研究了 NPs 的命运，包括血液清除和库普弗细胞摄取，最大浓度（）、血浆浓度-时间曲线下面积（AUC）和平均驻留时间（MRT）呈负线性相关，而库普弗细胞摄取与呈正线性相关。随后，我们使用聚（甲氧基乙基乙烯磷酸酯）-聚（dl-丙交酯）（PEEP-PLA）和聚（乙烯基吡咯烷酮）-聚（dl-丙交酯）（PVP-PLA）NPs 验证了该方法用于预测命运的可靠性，并且聚合物 NPs 的值与其 PK 参数之间的线性关系进一步表明，聚合物 NPs 的蛋白质结合亲和力可以直接指示其药代动力学。
