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Beyond tissue concentrations: antifungal penetration at the site of infection
Yanan Zhao1, Brendan Prideaux1, Shane Baistrocchi2
1Public Health Research Institute, New Jersey Medical School-Rutgers Biomedical and Health Sciences, Newark, NJ 07103.
Abstract:
Despite advances in antifungal therapy, invasive fungal infections remain a significant cause of morbidity and mortality worldwide. One important factor contributing to the relative ineffectiveness of existing antifungal drugs is insufficient drug exposure at the site of infection. Despite the importance of this aspect of antifungal therapy, we generally lack a full appreciation of how antifungal drugs distribute, penetrate, and interact with their target organisms in different tissue subcompartments. A better understanding of drug distribution will be critical to guide appropriate use of currently available antifungal drugs, as well as to aid development of new agents. Herein we briefly review current perspectives of antifungal drug exposure at the site of infection and describe a new technique, matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging, which has the potential to greatly expand our understanding of drug penetration.
Insights
Understanding antifungal drug distribution is key to improving treatment for invasive fungal infections. New imaging techniques like MALDI mass spectrometry can reveal how drugs penetrate tissues, aiding the development of more effective therapies.
Area of Science:
- Pharmacology
- Mycology
- Infectious Diseases
Background:
- Invasive fungal infections cause significant global morbidity and mortality.
- Current antifungal therapies are often limited by insufficient drug exposure at infection sites.
- Limited understanding exists regarding antifungal drug distribution and penetration within diverse tissue subcompartments.
Purpose of the Study:
- To review current knowledge on antifungal drug exposure at infection sites.
- To introduce matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging as a novel technique.
- To highlight the potential of MALDI-MS imaging to enhance understanding of antifungal drug penetration.
Main Methods:
- Review of existing literature on antifungal drug exposure.
- Description of matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging technique.
- Discussion of the application of MALDI-MS imaging in studying drug distribution.
Main Results:
- Current understanding of antifungal drug distribution in tissues is incomplete.
- MALDI-MS imaging offers unprecedented spatial resolution for drug distribution analysis.
- This technique can visualize drug concentrations in various tissue microenvironments.
Conclusions:
- Improved understanding of antifungal drug distribution is critical for optimizing current therapies.
- MALDI-MS imaging presents a powerful new tool for investigating drug penetration and exposure.
- Further research using MALDI-MS imaging can guide the development of novel antifungal agents with enhanced efficacy.
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