Abstract
The phosphorylation of (+) alpha tocopherol produces adhesive nanostructures that interact with oral biofilms to restrict their growth. The aim of this work was to understand if these adhesive (+) alpha tocopheryl phosphate (α-TP) nanostructures could also control macrophage responses to the presence of oral bacteria. The (+) α-TP planar bilayer fragments (175 nm ± 21 nm) formed in a Trizma®/ethanol vehicle swelled when exposed to the cell lines (maximum stabilized size = 29 μm). The swelled (+) α-TP aggregates showed selective toxicity towards THP-1 macrophages (LD50 = 304 μM) compared to human gingival fibroblasts (HGF-1 cells; LD50 > 5 mM), and they inhibited heat killed bacteria stimulated MCP-1 production in both macrophages (control 57.3 ± 18.1 pg/mL vs (+) α-TP 6.5 ± 3.2 pg/mL) and HGF-1 cells (control 673.5 ± 133 pg/mL vs (+) α-TP - 463.9 ± 68.9 pg/mL).
Highlights
Macrophages perform a number of important regulatory functions in the human body,[1] but in several pathologies including, malignant tumors,[2] inflammatory disease,[3] metabolic disease,[4] infections,[5] and periodontitis,[6] their dysfunction is thought to contribute to disease progression.[7]
Macrophages are highly mobile and they are difficult to target through traditional drug delivery approaches.[9]. Their ability to actively recognize and phagocytose foreign material provides a Funding information: The study was financed by an Engineering and Physical Sciences Research Council (EPSRC) CASE award with Johnson and Johnson
EPSRC had no role in study design, data collection and interpretation, or the decision to submit the work for publication
Summary
Macrophages perform a number of important regulatory functions in the human body,[1] but in several pathologies including, malignant tumors,[2] inflammatory disease,[3] metabolic disease,[4] infections,[5] and periodontitis,[6] their dysfunction is thought to contribute to disease progression.[7]. EPSRC had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Johnson and Johnson had a role in some experimental design and data interpretation. One class of lipids that have the potential to be formed into materials that could target macrophages is the tocopherol lipids.[10]. In recent work a novel tocopherol analogue, (+) alpha tocopheryl phosphate (α-TP) was synthesized and was shown to form oral bioretentive nanomaterials that disrupt biofilm growth.[11] In the mouth the ionic phosphate moiety of α-TP interacts with simple electrolytes and this gives it the potential to swell and change shape,[12] which could facilitate macrophage phagocytosis and release of the active from the nanomaterial structure.
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