In this special feature article, Steve Castellino and co‐authors highlight why matrix‐assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) technology is an important innovation, which can improve and enhance drug discovery and development. Currently, most IMS studies conducted in drug discovery and development focus on the quantitative distribution of drug candidates and their metabolites in animal model tissues. The need to understand the biodistribution of drugs in tissues is not a new concept, but historically, the analytical tools available to achieve this were limited. The introduction of IMS has addressed this gap by providing the ability to quantitatively characterize the distribution of drugs within tissues providing direct evidence of whether the drug is reaching the intended target. Thus, the aim of this special feature article is to share the authors collective experience in designing, conducting, and delivering impactful results using IMS in the preclinical space of pharmaceutical discovery and development. Dr. Stephen Castellino is currently Chief Analytics Officer at Glycopath (Charleston, South Carolina, USA). Dr Nichole M. Lareau is a Senior investigator and Dr Mark Reid Groseclose a Director in the Bioimaging group of GlaxoSmithKline (Collegeville, Pennsylvania, USA).
Liposomes are promising targeted drug delivery systems with the potential to improve the efficacy and safety profile of certain classes of drugs. Though attractive, there are unique analytical challenges associated with the development of liposomal drugs including human dose prediction given these are multi-component drug delivery systems. In this study, we developed a multimodal imaging approach to provide a comprehensive distribution assessment for an antibacterial drug, GSK2485680, delivered as a liposomal formulation (Lipo680) in a mouse thigh model of bacterial infection to support human dose prediction. Positron emission tomography (PET) imaging was used to track the in vivo biodistribution of Lipo680 over 48h post-injection providing a clear assessment of the uptake in various tissues and, importantly, the selective accumulation at the site of infection. In addition, a pharmacokinetic model was created to evaluate the kinetics of Lipo680 in different tissues. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) was then used to analyze and quantify the distribution of GSK2485680 and a liposomal lipid throughout sections of infected and non-infected thigh tissues at high spatial resolution. Through the combination of both PET and MALDI images, we observed an excellent correlation between the Lipo680-radionuclide signal from PET with GSK2485680 and lipid component signals from MALDI IMS. This multimodal translational method can reduce drug attrition by providing comprehensive biodistribution profiles of drug delivery systems to provide mechanistic insight and elucidate safety concerns. Liposomal formulations have broad potential to deliver therapeutics for other indications, and this work serves as a template to aid in delivering future liposomal drugs to the clinic.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.