Surfactant-Assisted Distal Pulmonary Distribution of Budesonide Revealed by Mass Spectrometry Imaging

Direct lung administration of budesonide in combination with surfactant reduces the incidence of bronchopulmonary dysplasia. Although the therapy is currently undergoing clinical development, the lung distribution of budesonide throughout the premature neonatal lung has not yet been investigated. Here, we applied mass spectrometry imaging (MSI) to investigate the surfactant-assisted distal lung distribution of budesonide. Unlabeled budesonide was either delivered using saline as a vehicle (n = 5) or in combination with a standard dose of the porcine surfactant Poractant alfa (n = 5). These lambs were ventilated for one minute, and then the lungs were extracted for MSI analysis. Another group of lambs (n = 5) received the combination of budesonide and Poractant alfa, followed by two hours of mechanical ventilation. MSI enabled the label-free detection and visualization of both budesonide and the essential constituent of Poractant alfa, the porcine surfactant protein C (SP-C). 2D ion intensity images revealed a non-uniform distribution of budesonide with saline, which appeared clustered in clumps. In contrast, the combination therapy showed a more homogeneous distribution of budesonide throughout the sample, with more budesonide distributed towards the lung periphery. We found similar distribution patterns for the SP-C and budesonide in consecutive lung tissue sections, indicating that budesonide was transported across the lungs associated with the exogenous surfactant. After two hours of mechanical ventilation, the budesonide intensity signal in the 2D ion intensity maps dropped dramatically, suggesting a rapid lung clearance and highlighting the relevance of achieving a uniform surfactant-assisted lung distribution of budesonide early after delivery to maximize the anti-inflammatory and maturational effects throughout the lung.

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Exemplifying the Screening Power of Mass Spectrometry Imaging over Label-Based Technologies for Simultaneous Monitoring of Drug and Metabolite Distributions in Tissue Sections

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057115623740 ◽

2015 ◽

Vol 21 (2) ◽

pp. 187-193 ◽

Cited By ~ 20

Author(s):

Richard J. A. Goodwin ◽

Anna Nilsson ◽

C. Logan Mackay ◽

John G. Swales ◽

Maria K. Johansson ◽

...

Keyword(s):

Mass Spectrometry ◽

Mass Spectrometry Imaging ◽

Cyclic Peptide ◽

Analysis Data ◽

Resolving Power ◽

High Mass ◽

Whole Body ◽

Ion Cyclotron Resonance ◽

Label Free ◽

Tissue Sections

Mass spectrometry imaging (MSI) provides pharmaceutical researchers with a suite of technologies to screen and assess compound distributions and relative abundances directly from tissue sections and offer insight into drug discovery–applicable queries such as blood-brain barrier access, tumor penetration/retention, and compound toxicity related to drug retention in specific organs/cell types. Label-free MSI offers advantages over label-based assays, such as quantitative whole-body autoradiography (QWBA), in the ability to simultaneously differentiate and monitor both drug and drug metabolites. Such discrimination is not possible by label-based assays if a drug metabolite still contains the radiolabel. Here, we present data exemplifying the advantages of MSI analysis. Data of the distribution of AZD2820, a therapeutic cyclic peptide, are related to corresponding QWBA data. Distribution of AZD2820 and two metabolites is achieved by MSI, which [14C]AZD2820 QWBA fails to differentiate. Furthermore, the high mass-resolving power of Fourier transform ion cyclotron resonance MS is used to separate closely associated ions.

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MALDIViz: A Comprehensive Informatics Tool for MALDI-MS Data Visualization and Analysis

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/2472555217727517 ◽

2017 ◽

Vol 22 (10) ◽

pp. 1246-1252 ◽

Cited By ~ 1

Author(s):

Kishore Kumar Jagadeesan ◽

Simon Ekström

Keyword(s):

Mass Spectrometry ◽

High Throughput ◽

High Throughput Screening ◽

Web Application ◽

Low Cost ◽

Maldi Ms ◽

Ionization Mass ◽

Label Free ◽

Label Free Detection ◽

R Shiny

Recently, mass spectrometry (MS) has emerged as an important tool for high-throughput screening (HTS) providing a direct and label-free detection method, complementing traditional fluorescent and colorimetric methodologies. Among the various MS techniques used for HTS, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) provides many of the characteristics required for high-throughput analyses, such as low cost, speed, and automation. However, visualization and analysis of the large datasets generated by HTS MALDI-MS can pose significant challenges, especially for multiparametric experiments. The datasets can be generated fast, and the complexity of the experimental data (e.g., screening many different sorbent phases, the sorbent mass, and the load, wash, and elution conditions) makes manual data analysis difficult. To address these challenges, a comprehensive informatics tool called MALDIViz was developed. This tool is an R-Shiny-based web application, accessible independently of the operating system and without the need to install any program locally. It has been designed to facilitate easy analysis and visualization of MALDI-MS datasets, comparison of multiplex experiments, and export of the analysis results to high-quality images.

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Impedimetric Immunosensor Utilizing Polyaniline/Gold Nanocomposite-Modified Screen-Printed Electrodes for Early Detection of Chronic Kidney Disease

Sensors ◽

10.3390/s19183990 ◽

2019 ◽

Vol 19 (18) ◽

pp. 3990 ◽

Cited By ~ 5

Author(s):

Muhammad Omar Shaikh ◽

Boyanagunta Srikanth ◽

Pei-Yu Zhu ◽

Cheng-Hsin Chuang

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Early Detection ◽

Electrochemical Impedance ◽

High Specificity ◽

Homogeneous Distribution ◽

Label Free ◽

Gold Nanocrystals ◽

Working Electrode ◽

Label Free Detection

The presence of small amounts of human serum albumin (HSA) in urine or microalbuminuria (30–300 µg/mL) is a valuable clinical biomarker for the early detection of chronic kidney disease (CKD). Herein, we report on the development of an inexpensive and disposable immunosensor for the sensitive, specific, and label-free detection of HSA using electrochemical impedance spectroscopy (EIS). We have utilized a simple one-step screen-printing protocol to fabricate the carbon-based three-electrode system on flexible plastic substrates. To enable efficient antibody immobilization and improved sensitivity, the carbon working electrode was sequentially modified with electropolymerized polyaniline (PANI) and electrodeposited gold nanocrystals (AuNCs). The PANI matrix serves as an interconnected nanostructured scaffold for homogeneous distribution of AuNCs and the resulting PANI/AuNCs nanocomposite synergically improved the immunosensor response. The PANI/AuNCs-modified working electrode surface was characterized using scanning electron microscopy (SEM) and the electrochemical response at each step was analyzed using EIS in a ferri/ferrocyanide redox probe solution. The normalized impedance variation during immunosensing increased linearly with HSA concentration in the range of 3–300 µg/mL and a highly repeatable response was observed for each concentration. Furthermore, the immunosensor displayed high specificity when tested using spiked sample solutions containing different concentrations of actin protein and J82 cell lysate (a complex fluid containing a multitude of interfering proteins). Consequently, these experimental results confirm the feasibility of the proposed immunosensor for early diagnosis and prognosis of CKD at the point of care.

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A Strategy for Label-free Visualization of Tissue Distribution of Green Tea Polyphenols Using Mass Spectrometry Imaging Technique

Oleoscience ◽

10.5650/oleoscience.17.489 ◽

2017 ◽

Vol 17 (10) ◽

pp. 489-495

Author(s):

Yoshinori FUJIMURA ◽

Daisuke MIURA ◽

Hirofumi TACHIBANA

Keyword(s):

Mass Spectrometry ◽

Tissue Distribution ◽

Green Tea ◽

Mass Spectrometry Imaging ◽

Imaging Technique ◽

Tea Polyphenols ◽

Green Tea Polyphenols ◽

Label Free

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Quantitative Mass Spectrometry Imaging of Biological Systems

Annual Review of Physical Chemistry ◽

10.1146/annurev-physchem-061020-053416 ◽

2021 ◽

Vol 72 (1) ◽

Author(s):

Daisy Unsihuay ◽

Daniela Mesa Sanchez ◽

Julia Laskin

Keyword(s):

Mass Spectrometry ◽

Mass Spectrometry Imaging ◽

Matrix Effects ◽

High Sensitivity ◽

Biological Tissues ◽

Annual Review ◽

Publication Date ◽

Label Free ◽

Complex Samples ◽

Mass Dependent

Mass spectrometry imaging (MSI) is a powerful, label-free technique that provides detailed maps of hundreds of molecules in complex samples with high sensitivity and subcellular spatial resolution. Accurate quantification in MSI relies on a detailed understanding of matrix effects associated with the ionization process along with evaluation of the extraction efficiency and mass-dependent ion losses occurring in the analysis step. We present a critical summary of approaches developed for quantitative MSI of metabolites, lipids, and proteins in biological tissues and discuss their current and future applications. Expected final online publication date for the Annual Review of Physical Chemistry, Volume 72 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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