Uptake of Vitamins D2, D3, D4, D5, D6, and D7 Solubilized in Mixed Micelles by Human Intestinal Cells, Caco-2, an Enhancing Effect of Lysophosphatidylcholine on the Cellular Uptake, and Estimation of Vitamins D’ Biological Activities

Abstract

Vitamins D have various biological activities, as well as intestinal calcium absorption. There has been recent concern about insufficient vitamin D intake. In addition to vitamins D2 and D3, there are lesser-known vitamins D4–D7. We synthesized vitamins D5–D7, which are not commercially available, and then evaluated and compared the mixed micelles-solubilized vitamins D uptake by Caco-2 cells. Except for vitamin D5, the uptake amounts of vitamins D4–D7 by differentiated Caco-2 cells were similar to those of vitamins D2 and D3. The facilitative diffusion rate in the ezetimibe inhibited pathway was approximately 20% for each vitamin D type, suggesting that they would pass through the pathway at a similar rate. Lysophosphatidylcholine enhanced each vitamin D uptake by approximately 2.5-fold. Lysophosphatidylcholine showed an enhancing effect on vitamin D uptake by reducing the intercellular barrier formation of Caco-2 cells by reducing cellular cholesterol, suggesting that increasing the uptakes of vitamins D and/or co-ingesting them with lysophosphatidylcholine, would improve vitamin D insufficiency. The various biological activities in the activated form of vitamins D4–D7 were estimated by Prediction of Activity Spectra for Substances (PASS) online simulation. These may have some biological activities, supporting the potential as nutritional components.

Designing Vitamin D3 Formulations: An In Vitro Investigation Using a Novel Micellar Delivery System

“…Significantly, Caco-2 permeability experiments showed that LipoMicel ® is 12,000 times more permeable compared to the baseline control (Table 3 and Figure 4). This is several orders of magnitude higher than the 2.5 times enhanced uptake reported on lysophosphatidylcholine micelles [30], the 4-fold increase in bioavailability reported in a casein micelles [47] and the 5.3-fold increase reported in pea-protein-based nanoemulsions [48]. However, in this study it appears that the increased permeability of micellar Vitamin D 3 does not correlate with increased solubility or reduced particle size-since LipoMicel has similar solubility characteristics (Figure 2) and particle size distribution (Figure 5 and Table 4) as the baseline control.…”

“…Efforts in this regard have generally been directed toward increasing solubilities by reducing the particle size of the delivery vehicles and creating nanoparticles and nanostructured lipid carriers [27][28][29]. However, in addition to particle size, there is increasing evidence that cell-matrix adhesion and specific receptor carriers may also play key roles in influencing absorption by using micellar delivery systems [30][31][32].…”

“…LipoMicel is used to improve the solubility and stability of various compounds by encapsulating the active compound in a lipid-based matrix and creating a natural emulsion. Although other micellar formulations have been previously reported, this study focuses on the investigation of formulations using only "food grade", safe ingredients without milk allergens or the use of synthetic detergents and organic solvents [30,[33][34][35]. It is worthwhile to investigate novel food grade formulations since they use ingredients that are safe for human consumption and are most likely to enter the market as health supplements.…”

Drug Screening, Oral Bioavailability and Regulatory Aspects: A Need for Human Organoids

“…Within the enterocytes, lipids are resynthesized and assembled into chylomicrons and high density lipoproteins for secretion [47]. The physiological pathway of fat digestion and uptake has gained increasing attention in drug development, as micelles can act as nanocarriers promoting the oral absorption of hydrophobic drugs and nutrients [21,48,49], and association of drugs with chylomicrons might prevent metabolic inactivation by avoiding the hepatic first-pass liver metabolism, as chylomicrons are transported via the lymphatic circulation [4]. Alternatively, enterocyte lipid metabolism may be targeted pharmacologically to lower systemic lipid load and energy intake, thus affecting hyperlipidemia, obesity, metabolic syndrome, steatosis, insulin resistance, atherosclerosis and other disorders [5,47].…”

Organic Synthesis of New Secosteroids from Fucosterol, Its Intestinal Absorption by Caco-2 Cells, and Simulation of the Biological Activities of Vitamin D

“…A prior study sought to determine if it was possible to prevent a vitamin D deficiency by increasing the intake of vitamins D2-D7 [49]. For vitamin D to work in the body as a nutrient or functional ingredient, it must first be absorbed through the intestinal tract.…”