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Cyclodextrin‐based nanocarriers for alpha‐tocopheryl phosphate and regulatory activity in THP‐1 monocytes
Author(s) -
Zingg JeanMarc,
Stamatiou Christina,
Daunert Sylvia
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.800.2
Subject(s) - chemistry , thp1 cell line , nanocarriers , monocyte , caco 2 , biochemistry , microbiology and biotechnology , cell culture , biology , drug delivery , in vitro , genetics , organic chemistry
The vitamin E derivative, alpha‐tocopheryl phosphate (αTP), occurs in small amounts in plasma and animal tissues. Low amounts of αTP are also present in foods but the bioavailability as an intact molecule is very low, since most of it is hydrolyzed. So far no efficient mechanism of intact cellular αTP uptake and tissue distribution has been identified when compared to vitamin E (alpha‐tocopherol, αT). Since αTP has been reported to be more potent in regulating signal transduction and gene expression than αT (e.g. on atherosclerosis, inflammation), a more efficient system to deliver intact αTP to cells in tissues may be useful. Here we characterize the formation of complexes of αTP with the nanocarrier cyclodextrin (CD). αTP/CD formed soluble complexes in a 1 to 2 ratio and generated a homogenous white colloidal emulsion that stayed in homogenous suspension for weeks. The αTP/CD complex inhibited proliferation of THP‐1 monocytes and CaCo2 colon carcinoma cells slightly stronger than αTP. When compared to CD, the complex of αTP/CD extracted cholesterol from cellular membrane of cultured THP‐1 monocytes and HT29 intestinal epithelial cells with higher efficiency and was associated with delivery of αTP to these cells. The αTP/CD complex induced VEGF promoter activity in THP‐1 and HEK293 cells with slightly higher efficiency than αTP. Interestingly, αTP and αTP/CD also reduced the phagocytosis of fluorescent Staphylococcus aureus bioparticles in THP‐1 monocytes/macrophages. αTP/CD assembled to higher order complexes with three types of modified starches and chitosan. These higher complexes had a comparable activity in the above assays and therefore may be useful as protective vehicles for oral, dermal or ocular delivery or as deposit‐enhancer in mucosa for delivery across epithelia. Support or Funding Information 1R21AI124058‐01