NanoCelle™ D3 is developed from patent-protected nano-technology creating Vitamin D3 nanoparticles that are easily absorbed across the oral mucosal linning. NanoCelle™ D3 is indicated to assist in the management of medically diagnosed vitamin D deficiency. Vitamin D3 aids in dietary calcium and phosphorus absorption, important for maintaining healthy bone mineral density. Vitamin D3 binds to the vitamin D receptor (VDR), which is located on all body cells. Activation of the VDR has been shown to regulate hundreds of genes. Because immune cells have the VDR, vitamin D may also assist with immune system function. Vitamin D3 is a fat-soluble vitamin that is naturally synthesised in the body from sun exposure (ultraviolet light) however the amount of vitamin D production depends on geographic location, season, time of day and weather conditions. In addition, clothing habits, lifestyle, and workplace (e.g., indoor versus outdoor), sunscreen use, and sun avoidance practices have an impact on vitamin D synthesis. Vitamin D3 production is also determined by a persons skin type, as the darker pigmented the skin is the less vitamin D3 is produced.
In addition to its well-known classical effects in calcium/phosphate homeostasis, vitamin D is a potent regulator of many other vital physiological functions in the body beyond that of bone health such as immune regulation.1 Vitamin D3 (cholecalciferol) is naturally synthesised in the skin and may contribute to 80-90% of the vitamin D supply within the body but this is ultimately dependent on factors such as sun exposure, geographic latitude, season, clothing habits, sunscreen use and skin complexion. Dietary sources of vitamin D3 are limited but include fatty fish, fish liver oil, beef liver, egg yolk and milk.1,2 Cholecalciferol is biologically inert and must undergo two hydroxylation reactions, first within the liver to produce 25-hydroxyvitamin D [25(OH)D] also known as calcidiol, and then in the kidney to produce the active hormonal metabolite 1,25-dihydroxyvitamin D [1,25(OH)2D] also know as calcitriol.3,4 Further, 25(OH)D can be converted to 1,25(OH)2D in at least 10 extra-renal tissues including immune cells (macrophages, dendritic cells and B-lymphocytes) and also vascular smooth muscle cells and colonocytes.1
As a lipid-soluble compound, orally ingested cholecalciferol (D3) is naturally emulsified into lipid droplets and combined with bile salts, phospholipids and cholesterol to form micelles that enable absorption across in the intestinal mucosa. A fraction of D3 enters enterocytes via passive diffusion when delivered at pharmacological doses, but the main intracellular transport of D3 into the enterocyte is via binding the micelle to apical membrane transporters. Intestinal absorption of vitamin D3 varies between 55-99% (mean 78%) in healthy individuals2 but is decreased in individuals with conditions of malabsorption such as cystic fibrosis, inflammatory bowel disease, coeliac disease, biliary obstruction, pancreatic dysfunction and intestinal resection.5,6 Furthermore, disruption in the conversion of vitamin D metabolites to the active hormone will also impact vitamin D status within the body such as in chronic kidney disease.7
The micellization process of drugs and nutrients prior to ingestion produces nano-sized particles consisting of an inner hydrophobic core (drug/nutrient combined with lipid carrier or is itself lipid-soluble) with a hydrophilic outer shell (various surfactants) creating a water-soluble solution that interacts with the mucosal cells. Figure 1 demonstrates an example of micellizing the fat-soluble compound, beta-carotene.
NanoCelle™ D3 consists of cholecalciferol forming the hydrophobic core coated with hydrophilic compounds to obtain a particle size approximately 50 - 200 nm (0.05 – 0.2 micron) that is soluble in aqueous solution (Figure 2). The uptake of the micelle particles across the mucosal membrane and the extent of drug/nutrient absorption increases with decreasing particle size.8,9 Drug delivery via the oral mucosa by-passes the gastrointestinal tract and any conditions that may influence or inhibit its absorption across the intestinal mucosa.
NanoCelle™ D3: Hydrophobic polymer/drug molecule = cholecalciferol
The secosteroid hormone 1,25(OH)2D is the biologically active form of vitamin D3 and initiates physiological responses of more than 36 cell types that possess the vitamin D receptor (VDR) on their cell membrane or in the cytosol, by regulating gene transcription and activating signal transduction pathways similar to other steroid hormones.Cholecalciferol itself does not bind to the VDR. It is estimated that the VDR can regulate the expression of 3% of the human genome.10 It is well established that 1,25(OH)2D plays a vital role in adaptive and innate immune regulation from inducing the differentiation of monocytes into macrophages; increasing macrophage activity and cytotoxic activity; inducing the synthesis of the antibacterial proteins cathelicidin and beta-defensin; inducing IFN-gamma-mediated antimicrobial activity and regulating Th1, Th2, Treg and Th17 responses (Figure 3).
NanoCelle™ D3 is a nano-particle formulation that may: