Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy
The efficacy and potential toxicity of drug treatments depends on the drug concentration at its site of action, intricately linked to its distribution within diverse organelles of mammalian cells. These organelles, including the nucleus, endosome, lysosome, mitochondria, endoplasmic reticulum, Golgi...
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MDPI AG
2024-09-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/16/9/1167 |
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| author | Xin Liu Miaomiao Li Sukyung Woo |
| author_facet | Xin Liu Miaomiao Li Sukyung Woo |
| author_sort | Xin Liu |
| collection | DOAJ |
| description | The efficacy and potential toxicity of drug treatments depends on the drug concentration at its site of action, intricately linked to its distribution within diverse organelles of mammalian cells. These organelles, including the nucleus, endosome, lysosome, mitochondria, endoplasmic reticulum, Golgi apparatus, lipid droplets, exosomes, and membrane-less structures, create distinct sub-compartments within the cell, each with unique biological features. Certain structures within these sub-compartments possess the ability to selectively accumulate or exclude drugs based on their physicochemical attributes, directly impacting drug efficacy. Under pathological conditions, such as cancer, many cells undergo dynamic alterations in subcellular organelles, leading to changes in the active concentration of drugs. A mechanistic and quantitative understanding of how organelle characteristics and abundance alter drug partition coefficients is crucial. This review explores biological factors and physicochemical properties influencing subcellular drug distribution, alongside strategies for modulation to enhance efficacy. Additionally, we discuss physiologically based computational models for subcellular drug distribution, providing a quantifiable means to simulate and predict drug distribution at the subcellular level, with the potential to optimize drug development strategies. |
| format | Article |
| id | doaj-art-13f9d2b9d96248d981932d5a3df943ca |
| institution | OA Journals |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-13f9d2b9d96248d981932d5a3df943ca2025-08-20T01:55:46ZengMDPI AGPharmaceutics1999-49232024-09-01169116710.3390/pharmaceutics16091167Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic EfficacyXin Liu0Miaomiao Li1Sukyung Woo2Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY 14214-8033, USADivision of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH 43210-1267, USADepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY 14214-8033, USAThe efficacy and potential toxicity of drug treatments depends on the drug concentration at its site of action, intricately linked to its distribution within diverse organelles of mammalian cells. These organelles, including the nucleus, endosome, lysosome, mitochondria, endoplasmic reticulum, Golgi apparatus, lipid droplets, exosomes, and membrane-less structures, create distinct sub-compartments within the cell, each with unique biological features. Certain structures within these sub-compartments possess the ability to selectively accumulate or exclude drugs based on their physicochemical attributes, directly impacting drug efficacy. Under pathological conditions, such as cancer, many cells undergo dynamic alterations in subcellular organelles, leading to changes in the active concentration of drugs. A mechanistic and quantitative understanding of how organelle characteristics and abundance alter drug partition coefficients is crucial. This review explores biological factors and physicochemical properties influencing subcellular drug distribution, alongside strategies for modulation to enhance efficacy. Additionally, we discuss physiologically based computational models for subcellular drug distribution, providing a quantifiable means to simulate and predict drug distribution at the subcellular level, with the potential to optimize drug development strategies.https://www.mdpi.com/1999-4923/16/9/1167subcellular drug distributiondrug resistancedrug efficacyorganelle targetingcomputational pharmacokinetic modeling |
| spellingShingle | Xin Liu Miaomiao Li Sukyung Woo Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy Pharmaceutics subcellular drug distribution drug resistance drug efficacy organelle targeting computational pharmacokinetic modeling |
| title | Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy |
| title_full | Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy |
| title_fullStr | Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy |
| title_full_unstemmed | Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy |
| title_short | Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy |
| title_sort | subcellular drug distribution exploring organelle specific characteristics for enhanced therapeutic efficacy |
| topic | subcellular drug distribution drug resistance drug efficacy organelle targeting computational pharmacokinetic modeling |
| url | https://www.mdpi.com/1999-4923/16/9/1167 |
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