Targeting macrophages with biomass-derived nanoparticles for enhanced anti-inflammatory effects of curcuminoids
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Résumé
Introduction: Plants naturally synthesize nanoparticles to transport cellular materials that contain potential active pharmaceutical ingredients (APIs). Curcuminoids, including curcumin (the most abundant), demethoxycurcumin, and bisdemethoxycurcumin, are the primary active pharmaceutical ingredients (APIs) in turmeric root (from the Curcuma longa plant), a traditional medicine with antioxidative and anti-inflammatory effects. Numerous chronic diseases are associated with elevated oxidative stress and inflammation, centring around macrophage biology. Nano-encapsulation of curcumin can improve its stability, solubility and bioavailability to target highly phagocytic macrophages and exert anti-inflammatory effects by induction of cytoprotective heme-oxygenase-1 (HMOX1) and attenuation of inflammatory cytokine release (IFN-α, IL-6, TNF-α). Hypothesis: Turmeric root extruded nanoparticle curcumin (PVDL-005) will elicit greater direct antioxidative and/or indirect cytoprotective effects via curcumin-mediated HMOX1 induction and attenuation of inflammatory cytokine release (IFN-α, IL-6, TNF-α) in human macrophages compared to a molar equivalent amount of curcumin. Methods: Hydrodynamic size and zeta-potential surface charge of PVDL-005 were performed with Malvern dynamic light scattering for routine QAC; electron microscopy and Ultra Performance Liquid Chromatography (UPLC) confirmed nanoparticle size and shape, with API content (described as total curcuminoids), respectively. Ferric Reducing Antioxidant Power (FRAP) assay measured total antioxidant capacity and resazurin viability assay to measure LD 50 . To examine and compare PVDL-005 and soluble curcumin effects on macrophages, we used the THP-1 human monocyte cell lines differentiated into human macrophages. Western Blot measured HMOX1 expression levels. Confocal microscopy showed nanoparticle intracellular localization, and flow cytometry measured the uptake-internalization kinetics of PVDL-005 and soluble curcumin. Macrophages were pre-treated with PVDL-005 or soluble curcumin followed by LPS and inflammatory cytokines, and then ELISA and qPCR were used to measure the cytokine levels and expression. Results: PVDL-005 is spherical, with a size and surface charge of 177 nm and -0.189 mV, respectively. UPLC showed that the total curcuminoid concentration of formulated PVDL-005 and soluble curcumin was [2031µM] and [1570µM], respectively. PVDL-005 had a slight LD 50 ([10.3µM]) safety advantage over soluble curcumin ([6.9µM]), exhibited similar direct antioxidant activity by FRAP assay and induced HMOX1 expression. PVDL-005 [5µM] eq was internalized by macrophages with more significant and rapid uptake than soluble curcumin over 24hrs. Pre-treatment of macrophages with [5µM] eq PVDL-005 or [5µM] curcumin for 0.5hr followed by LPS exposure for 4hr show PVDL-005 attenuated inflammatory IFN-α levels more than soluble curcumin. Conclusion: Harnessing natural extrusion nanoformulation could enhance the stability and intrinsic properties of API by nano-encapsulation for safe augmented cell-targeted drug delivery. NSERC, Mitacs, Pividl Inc., Dalhousie Medical Research Foundation This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
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