Visualisation of drug delivery by using high resolution microscopic mass spectrometry

DOI Web Site オープンアクセス

この論文をさがす

説明

Background: Pharmacokinetic (PK) and pharmacodynamic (PD) studies are important to evaluate the efficacy and toxicity of the drugs. In these analyses, tissue homogenates are generally used for the quantification by high-performance liquid chromatography (HPLC) or liquid chromatography mass spectrometry (LC-MS). However, they lack the drug distribution in a specific anatomical area. The precise information about the distribution allows the researchers to optimize the drug design enabling more efficient targeted delivery.<br><br>Purpose: We studied the tissue distribution of paclitaxel (PTX) and its micellar formulation (NK105) using a microscopic mass spectroscopy (MMS).<br><br>Method: A MMS in which a microscope is coupled with an atmospheric pressure matrix-assisted laser desorption/ionization (MALDI) and quadruple ion trap time-of-flight (TOF) analyser was used. The matrix-coated drug sample is ionised and then separated on the basis of its mass-to-charge ratio (m/z). Images were acquired from imaging mass spectrometry (IMS) or tandem mass spectrometry (MS/MS) data.<br><br>Result: (1) We established the drug imaging system with enhanced resolution and sensitivity. In the analysis, MS and MS/MS were used for quantification and validation, respectively. (2) NK105 showed much stronger antitumor effects on a human pancreatic cancer BxPC3 xenograft than PTX. In the drug imaging, we demonstrated that NK105 delivered more PTX to the whole tumor tissue (including the center lesion). In the mouse model, PTX caused the peripheral neurotoxicity but NK105 did not. Multiple high drug-signal areas surrounding and inside the caudal nerve were observed in the case of PTX, whereas the signals after NK105 injection were significantly low.<br><br>Conclusion: We succeeded in corroborating the EPR effect using MMS. The data obtained by the drug imaging may be useful for facilitating DDS-drug design.

収録刊行物

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ