Real time measurement of PEG shedding from lipid nanoparticles in serum via NMR spectroscopy.
Real time measurement of PEG shedding from lipid nanoparticles in serum via NMR spectroscopy.
复制标题
通过核磁共振波谱法实时测量血清中脂质纳米颗粒的 PEG 脱落。
作者：
Stephen C Wilson;J. Baryza;A. J. Reynolds;K. Bowman;M. Keegan;S. Standley;Noah P. Gardner;P. Parmar;Vahide Ozlem Agir;S. Yadav;Adnan Zunic;C. Vargeese;Cameron C. Lee;S. Rajan
小干扰RNA（siRNA）是一种新型的治疗方式，其受益于纳米颗粒介导的递送。临床上最先进的含siRNA的纳米颗粒是siRNA和脂质（脂质纳米颗粒或LNP）的聚合物包被的超分子组装体，其保护siRNA免受核酸酶的影响，调节siRNA的药代动力学，并使siRNA能够选择性递送至靶细胞。理解这样的系统的组装和递送的机制是复杂的动态超分子组装的复杂性，以及其随后与生物环境的相互作用。我们已经开发了一种离体方法，该方法提供了对LNP在与生物流体接触时如何表现的深入了解。脉冲梯度自旋回波（PGSE）NMR用于直接测量大鼠血清中siRNA包封的LNP的聚乙二醇（PEG）脱落动力学。该方法代表了一种分子特异性、实时、定量和无标记的方法来监测纳米颗粒表面涂层的行为。我们认为，这种方法具有广泛的影响，在获得机制的见解如何纳米颗粒为基础的药物输送车辆在生物流体中的行为，是通用的，足以适用于多种系统。
Small interfering RNA (siRNA) is a novel therapeutic modality that benefits from nanoparticle mediated delivery. The most clinically advanced siRNA-containing nanoparticles are polymer-coated supramolecular assemblies of siRNA and lipids (lipid nanoparticles or LNPs), which protect the siRNA from nucleases, modulate pharmacokinetics of the siRNA, and enable selective delivery of siRNA to target cells. Understanding the mechanisms of assembly and delivery of such systems is complicated by the complexity of the dynamic supramolecular assembly as well as by its subsequent interactions with the biological milieu. We have developed an ex vivo method that provides insight into how LNPs behave when contacted with biological fluids. Pulsed gradient spin echo (PGSE) NMR was used to directly measure the kinetics of poly(ethylene) glycol (PEG) shedding from siRNA encapsulated LNPs in rat serum. The method represents a molecularly specific, real-time, quantitative, and label-free way to monitor the behavior of a nanoparticle surface coating. We believe that this method has broad implications in gaining mechanistic insights into how nanoparticle-based drug delivery vehicles behave in biofluids and is versatile enough to be applied to a diversity of systems.
影响因子：
12.4
作者：
Akinc, Akin;Goldberg, Michael;Anderson, Daniel G.
通讯作者：
Anderson, Daniel G.
影响因子：
16.6
作者：
Gao, Weiwei;Langer, Robert;Farokhzad, Omid C.
通讯作者：
Farokhzad, Omid C.
DOI：
10.1016/0005-2760(84)90156-5
发表时间：
1984-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
MASSEY, JB;HICKSON, D;POWNALL, HJ
通讯作者：
POWNALL, HJ