1H–19F cross-polarization magic angle spinning dynamic nuclear polarization NMR investigation of advanced pharmaceutical formulations

IF 2 3区 化学 Q3 BIOCHEMICAL RESEARCH METHODS
Mária Šoltésová , Arthur C. Pinon , Fabien Aussenac , Judith Schlagnitweit , Christian Reiter , Armin Purea , Roberto Melzi , Frank Engelke , Dave Martin , Stefanie Krambeck , Annabelle Biscans , Emma Kay , Lyndon Emsley , Staffan Schantz
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Abstract

A new 3.2 mm 1H–19F–X magic angle spinning dynamic nuclear polarization NMR (MAS DNP-NMR) probe was developed with a unique coil design with separate radiofrequency channels for 1H excitation and 13C or 19F detection to enable acquisition of 1H–19F cross-polarization (CP) MAS experiments, direct-detected 19F spectra with proton decoupling, and acquisition on 13C with simultaneous double decoupling on the 1H and 19F channels as well as 1H–19F–13C double-CP experiments under low temperature MAS DNP conditions. We use these sequences to study AZD2811, which is an active pharmaceutical ingredient (API), in its pure dry state as well as in its corresponding drug delivery formulation consisting of drug-loaded polymeric nanoparticles (PNPs). Included in this study are also small interfering RNAs (siRNAs) for therapeutic targeting of peptidyl-prolyl cis–trans isomerase B (Ppib) mRNA. We demonstrate that 1H–19F CP MAS experiments performed on the new HFX probe represent a notable advantage over usually acquired direct-detected 19F experiments. The indirect 19F DNP enhancement εon/off(19F) = 26 was obtained via 1H–19F CP for the pure API impregnated with DNP solution, with an overall 30-fold sensitivity gain compared to the direct-detected 19F experiment under similar conditions. DNP enhancement value of εon/off(19F) = 42 was obtained via 1H–19F CP for the polymeric nanoparticle suspension and εon/off(19F) ≈ 150 were obtained for two different siRNAs in frozen DNP solution.

Abstract Image

h - 19f交叉极化魔角自旋动态核极化核磁共振研究先进药物配方。
研制了一种新型3.2 mm 1H-19F- x魔角自旋动态核极化NMR (MAS DNP-NMR)探针,该探针具有独特的线圈设计,具有用于1H激励和13C或19F检测的独立射频通道,能够采集1H-19F交叉极化(CP) MAS实验,直接检测质子去耦的19F光谱。在1H和19F通道同时双去耦的13C采集以及低温MAS DNP条件下1H-19F-13C双cp实验。我们使用这些序列来研究AZD2811,它是一种活性药物成分(API),在其纯干燥状态下,以及由载药聚合物纳米颗粒(PNPs)组成的相应的给药配方。本研究还包括用于治疗肽酰脯氨酸顺式反式异构酶B (Ppib) mRNA的小干扰rna (sirna)。我们证明,在新的HFX探针上进行的1H-19F CP MAS实验比通常获得的直接检测19F实验具有显着优势。用1H-19F CP对浸有DNP溶液的纯API进行间接19F DNP增强,得到了间接19F DNP增强εon/off(19F) = 26,与在相同条件下直接检测19F实验相比,总体灵敏度提高了30倍。聚合物纳米颗粒悬浮液通过1H-19F CP得到DNP增强值εon/off(19F) = 42,两种sirna在DNP冷冻溶液中得到εon/off(19F)≈150。
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来源期刊
CiteScore
3.80
自引率
13.60%
发文量
150
审稿时长
69 days
期刊介绍: The Journal of Magnetic Resonance presents original technical and scientific papers in all aspects of magnetic resonance, including nuclear magnetic resonance spectroscopy (NMR) of solids and liquids, electron spin/paramagnetic resonance (EPR), in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS), nuclear quadrupole resonance (NQR) and magnetic resonance phenomena at nearly zero fields or in combination with optics. The Journal''s main aims include deepening the physical principles underlying all these spectroscopies, publishing significant theoretical and experimental results leading to spectral and spatial progress in these areas, and opening new MR-based applications in chemistry, biology and medicine. The Journal also seeks descriptions of novel apparatuses, new experimental protocols, and new procedures of data analysis and interpretation - including computational and quantum-mechanical methods - capable of advancing MR spectroscopy and imaging.
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