| Autor: |
Wilson SC; Novartis Institutes for Biomedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States., Baryza JL, Reynolds AJ, Bowman K, Keegan ME, Standley SM, Gardner NP, Parmar P, Agir VO, Yadav S, Zunic A, Vargeese C, Lee CC, Rajan S |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular pharmaceutics [Mol Pharm] 2015 Feb 02; Vol. 12 (2), pp. 386-92. Date of Electronic Publication: 2015 Jan 12. |
| DOI: |
10.1021/mp500400k |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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