ArticleACS chemical biology2014
Colloidal drug formulations can explain "bell-shaped" concentration-response curves.
Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed.
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- An Overview of the Current State of Cell Viability Assessment Methods Using OECD Classification.International journal of molecular sciences · 2024Review
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- Unveiling the Potential of Natural Compounds: A Comprehensive Review on Adipose Thermogenesis Modulation.International journal of molecular sciences · 2024Review
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- The Potential of Congo Red Supplied Aggregates of Multitargeted Tyrosine Kinase Inhibitor (Sorafenib, BAY-43-9006) in Enhancing Therapeutic Impact on Bladder Cancer.International journal of molecular sciences · 2023Article
- Molecular design and synthesis of methoxy-substitued spiropyrans with photomodulated NIR-fluorescence.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2023Article
- Impact of adrenomedullin on mitochondrial respiratory capacity in human adipocyte.Scientific reports · 2023Article
- Synthetic Ionizable Colloidal Drug Aggregates Enable Endosomal Disruption.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Effect of Ovocystatin on Amyloid β 1-42 Aggregation-In Vitro Studies.International journal of molecular sciences · 2023Article
- Impact of Adrenomedullin on Mitochondrial Respiratory Capacity in Human Adipocyte.Research square · 2023Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
Abstract
Drug efficacy does not always increase sigmoidally with concentration, which has puzzled the community for decades. Unlike standard sigmoidal curves, bell-shaped concentration-response curves suggest more complex biological effects, such as multiple-binding sites or multiple targets. Here, we investigate a physical property-based mechanism for bell-shaped curves. Beginning with the observation that some drugs form colloidal aggregates at relevant concentrations, we determined concentration-response curves for three aggregating anticancer drugs, formulated both as colloids and as free monomer. Colloidal formulations exhibited bell-shaped curves, losing activity at higher concentrations, while monomeric formulations gave typical sigmoidal curves, sustaining a plateau of maximum activity. Inverting the question, we next asked if molecules with bell-shaped curves, reported in the literature, form colloidal aggregates at relevant concentrations. We selected 12 molecules reported to have bell-shaped concentration-response curves and found that five of these formed colloids. To understand the mechanism behind the loss of activity at concentrations where colloids are present, we investigated the diffusion of colloid-forming dye Evans blue into cells. We found that colloidal species are excluded from cells, which may explain the mechanism behind toxicological screens that use Evans blue, Trypan blue, and related dyes.
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