Vitamin tissue delivery

The specific role of vitamin A in tissue differentiation has been an active area of research. The current thinking, developed in 1979, involves initial delivery of retinol by o/o-RBP (retinol-binding protein) to the cell cytosol (66). Retinol is then ultimately oxidized to retinoic acid and binds to a specific cellular retinoid-binding protein and is transported to the nucleus. Retinoic acid is then transferred to a nuclear retinoic acid receptor (RAR), which enhances the expression of a specific region of the genome. Transcription occurs and new proteins appear during the retinoic acid-induced differentiation... 

Vitamin E deficiency occurs due to genetic defects in the formation of hepatic a-tocopherol transfer protein. This transport protein plays a central role in the liver and one of its functions is to facilitate incorporation of a-tocopherol into nascent very low density lipoproteins (VLDLs). Since there are no specific transport proteins for vitamin E in plasma, the delivery of vitamin E to the tissues is primarily mediated by VLDL-LDL transport mechanisms (Chapter 20). Thus, deficiency of hepatic a-tocopherol transport protein causes low plasma levels of vitamin E with impairment of delivery to the tissues. Patients with the transport protein deficiency exhibit peripheral neuropathy and ataxia. Early and vigorous vitamin E supplementation in patients with neurological symptoms and with low plas-mal levels of vitamin E has yielded therapeutic benefits. 

The first lipocalin whose 3-D structure was solved and refined at high resolution was the human plasma retinol-binding protein (RBP) [22, 23]. RBP acts as a natural transporter of vitamin A (retinol) in the blood of vertebrates. Upon complexation in a hydrophobic cavity with complementary shape, the poorly soluble terpenoid alcohol becomes packaged by the protein and protected from oxidation or double-bond isomerization. RBP is synthesized in the liver and directly loaded with fhe hgand in fhe hepatocyte, where retinol is stored. Furthermore, the holo-RBP forms a structurally defined ternary complex with transthyretin [24], also known as prealbumin. After delivery of the retinol ligand to a target tissue, fhe complex decomposes and fhe monomeric apo-RBP becomes filtered out by fhe kidney and degraded. 

Folate (vitamin Bg) is a low-molecular-weight (441 Da) compound essential in cell proliferation and for the biosynthesis of methionine, serine, deoxythymine add, and purine. Folate is internalized via two independent pathways either by transport of folate by the folate reeeptor or as 5-methyl-tetrahydrofolate by the reduced folate carrier. The expression of folate receptor (FR) in healthy tissue is limited to activated macrophages, placental cells, and the apical surface of polarized epithelia, where it is present in different isoforms [56]. The overexpression of FR on a broad range of solid tumors (ovary, lung, breast, kidney, brain, endometrium, and colon) makes it a suitable target for selective tumor drug delivery (for review, see [57J). 

The blend created for tissue engineering scaffolds can also be used as a material for drug delivery. Reddy et al7 reported the development of a bone filler and drug delivery vehicle using a bionanocomposite, which was filled with bone morphogenetic protein, which stimulates bone formation. Besides that, a hydro>yapatite/chitosan nanocomposite was used in the controlled release of vitamins from the matrix. The blending of PHAs could also be used in a similar way since they share the same features, such as the biocompatibility and not causing adverse effects, which produce desirable clinical outcomes. Chan et developed P(3HB)/EtC blends with a... 

Vitamin A is mobilized from the liver and delivered to peripheral target tissues as the retinol-RBP complex. Retinol mobilization and delivery are highly regulated processes that are particularly controlled by processes that regulate the rates of synthesis and secretion of RBP by the liver. Some information is available about the cellular and molecular mechanisms that mediate these phenomena. In addition, there is evidence that delivery of retinol to peripheral target tissues may involve specific cell-surface receptors that recognize RBP. 

Traber MG, Cohn W, Muller DP. Absorption, transport and delivery to tissues. In Lester P, Jurgen F, editors Vitamin E in health and disease. New York Marcel Dekker, Inc. 1993. p. 35-52. 

There is no evidence that vitamin E is transported in the plasma by a specific carrier protein, but rather it is nonspecifically transported in lipoproteins. An advantage of vitamin E transport in lipoproteins is that easily oxidizable lipids are protected by the simultaneous transport of this lipid-soluble antioxidant. Similarly, delivery of vitamin E to tissues is dependent upon lipid and lipoprotein metabolism. Thus, as peroxidizable lipids are taken up by tissue, the tissues simultaneously acquire a lipid-soluble antioxidant. 

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