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Microscopic Mass Spectrometry for the Precise Design of Drug Delivery Systems

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Intracellular Delivery III

Part of the book series: Fundamental Biomedical Technologies ((FBMT))

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Abstract

To bring drugs formulated in drug delivery systems (DDS) successfully into the clinic, preclinical studies have to be conducted which are aimed at obtaining pharmacological data relevant to the clinical application of such drugs. For such preclinical studies high-performance liquid chromatography (HPLC) or liquid chromatography mass spectrometry (LC-MS) is generally used. However, these methods do not generate data about the drug distribution in a specific target area, although obtained data allow optimizing the drug design in order to achieve a more efficient targeted delivery.

Microscopic mass spectrometry (MMS), in which a microscope is coupled to an atmospheric pressure matrix-assisted laser desorption/ionization (MALDI) and quadruple ion trap time-of-flight (TOF) analyzer has been developed for the investigation of the distribution of molecules such as small peptide metabolites and low-molecular weight drugs. The matrix-coated drug sample is ionized and then separated based on its mass-to-charge ratio (m/z). Images are acquired from imaging mass spectrometry or tandem mass spectrometry (MS/MS) data, respectively.

Here we introduce a drug imaging system with enhanced resolution and sensitivity which is based on using MMS. In our analysis, MS and MS/MS were used for quantification and validation, respectively. Our short review describes how the use of MMS allows the analysis of the precise distribution of a DDS drug complex including both, active and passive targeting systems. Notably, we successfully visualized and quantified the distribution of a non-radiolabeled and non-chemically modified drug in various frozen tissue slices microscopically.

In conclusion, MMS may provide a new strategy for facilitating the design of DDS with incorporated low-molecular weight drugs.

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Abbreviations

DDS:

Drug delivery system

MALDI:

Matrix-assisted laser desorption/ionization

MMS:

Microscopic mass spectrometry

EPR:

Enhanced permeability and retention

RES:

Reticuloendothelial system

ADC:

Antibody drug conjugate

ACA:

Anticancer agent

MMAE:

Monomethyl auristatin E

PTX:

Paclitaxel

CHCA:

α-cyano-4-hydroxycinnamic acid

DHB:

2,5-Dihydroxybenzoic acid

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Authors and Affiliations

  1. Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, 277-8577, Kashiwa, Japan

    Yasuhiro Matsumura & Masahiro Yasunaga

Authors
  1. Yasuhiro Matsumura
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  2. Masahiro Yasunaga
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Corresponding author

Correspondence to Yasuhiro Matsumura .

Editor information

Editors and Affiliations

  1. Biomolecular and Chemical Engineering, Vanderbilt University Biomolecular and Chemical Engineering, Nashville, Tennessee, USA

    Aleš Prokop

  2. Pharmaceutical Sciences, Midwestern University Pharmaceutical Sciences, GLENDALE, Arizona, USA

    Volkmar Weissig

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Matsumura, Y., Yasunaga, M. (2016). Microscopic Mass Spectrometry for the Precise Design of Drug Delivery Systems. In: Prokop, A., Weissig, V. (eds) Intracellular Delivery III. Fundamental Biomedical Technologies. Springer, Cham. https://doi.org/10.1007/978-3-319-43525-1_13

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