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Real Time Measurement of PEG Shedding from Lipid Nanoparticles in Serum via NMR Spectroscopy

Wilson, Stephen C. and Baryza, Jeremy and Reynolds, Aimee and Bowman, Keith and Keegan, Mark E. and Standley, Stephany and Gardner, Noah and Parmar, Parul and Agir, Vahide and Yadav, Sunita and Zunic, Adnan and Vargeese, Chandra and Lee, Cameron and Rajan, Srinivasan (2015) Real Time Measurement of PEG Shedding from Lipid Nanoparticles in Serum via NMR Spectroscopy. Molecular Pharmaceutics.

Abstract

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.

Item Type: Article
Keywords: PGSE NMR; LNP; lipid nanoparticle; nanoparticle; liposome; micelle; PEG shedding; PEG-lipid; siRNA
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/21738

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