Fatty acids delivery

Romijn, J. A., Coyle, E. R, Sidossis, L. S., et al., 1996. Relationship between fatty acid delivery and fatty acid oxidation during strenuous exercise. Journal of Applied Physiology 79 1939—1945. 

Omega-3 acids are considered essential to human health, but eannot be manufactured by the human body and must therefore be obtained from food. These acids are naturally present in most fishes and certain plant oils such as soybean and canola, which are foods that people rarely consume in large quantities. Moreover, the direct addition of omega-3 fatty acids to many foods is prevented due to some characteristics (fishy flavors, readily oxidized), which together reduce the sensory acceptability of foods containing fatty acids, limit shelf life, and potentially reduce the bioavailability of the acids. Encapsulation responds to the challenges of omega-3 fatty acid delivery and extends the reach of its health benefits. 

While most vesicles are formed from double-tail amphiphiles such as lipids, they can also be made from some single chain fatty acids [73], surfactant-cosurfactant mixtures [71], and bola (two-headed) amphiphiles [74]. In addition to the more common spherical shells, tubular vesicles have been observed in DMPC-alcohol mixtures [70]. Polymerizable lipids allow photo- or chemical polymerization that can sometimes stabilize the vesicle [65] however, the structural change in the bilayer on polymerization can cause giant vesicles to bud into smaller shells [76]. Multivesicular liposomes are collections of hundreds of bilayer enclosed water-filled compartments that are suitable for localized drug delivery [77]. The structures of these water-in-water vesicles resemble those of foams (see Section XIV-7) with the polyhedral structure persisting down to molecular dimensions as shown in Fig. XV-11. 

This compartment contains about one-third of total body water and is distributed between the plasma and interstitial compartments. The extracellular fluid is a delivery system. It brings to the cells nutrients (eg, glucose, fatty acids, amino acids), oxygen, various ions and trace minerals, and a variety of regulatory molecules (hormones) that coordinate the functions of widely separated cells. Extracellular fluid removes COj, waste... 

Transferosomes represent another system of encapsulation using ultradeformable vesicle carriers for bioactive molecules, applied until now for direct transdermal drug delivery. They are built from polar lipids and have high flexibility, and are rich in unsaturated fatty acids and carotenoid pigments." ... 

Abstract The biological effects of fullerenes and, in particular, of C60 have been recognized since long time. One of the problems which hindered the application of fullerenes in medicinal chemistry regards their insolubility in water and water-based fluids. In the present chapter it is reported that C60 and C70 fullerenes are soluble in vegetable oils, in general, in esters of fatty acids and in free fatty acids. These results pave the way in the utilization of vegetable oils as vehicles in the delivery of fullerenes for both topical applications and internal use (e.g., intramuscular injection). 

Keywords Adducts, C60, C70, esters of fatty acid, excipients, fatty acids, fullerenes, glycerol esters of fatty acids, grafting, group increment method, solubility, solubility parameter, vehicles for drug delivery, vegetable oils, triglycerides... 

The C60 and C70 reactivity with the vegetable oils at first glance could appear as an obstacle in the use of fullerene solutions in vegetable oils. Apart from the fact that one could use fully saturated fatty acids derivatives as vehicle for fullerenes delivery, which are not reactive with them, the formation of adducts between the unsaturated fatty acids and fullerenes could be exploited not only in the stabilization of the systems fullerenes-vegetable oils, but also in the alteration and, may be in the attenuation of the fullerene reactivity in in vivo and in a very gradual release of the fullerenes-fatty acids derivatives in living systems. 

Cano-Cebrian MJ, Zornoza T, Granero L, and Polache A (2005) Intestinal absorption enhancement via the paracellular route by fatty acids, chitosans and others A target for drug delivery. Curr. Drug Deliv. 2 9-22. 

The problems with this approach is that the intestinal pH may not be stable, since it is affected by diet, disease, and presence of fatty acids, carbon dioxide, and other fermentation products. Moreover, there is considerable difference in inter- and intraindividual gastrointestinal tract pH, which causes a major problem in reprodueible drug delivery to the large intestine [58]. 

Testosterone (T.) derivatives for clinical use. T. esters for im. depot injection are T. propionate and T. heptanoate (or enanthate). These are given in oily solution by deep intramuscular injection. Upon diffusion of the ester from the depot, esterases quickly split off the acyl residue, to yield free T. With increasing lipophilicity, esters will tend to remain in the depot, and the duration of action therefore lengthens. A T. ester for oral use is the undecanoate. Owing to the fatty acid nature of undecanoic acid, this ester is absorbed into the lymph, enabling it to bypass the liver and enter, via the thoracic duct, the general circulation. 17-0 Methyltestosterone is effective by the oral route due to its increased metabolic stability, but because of the hepatotoxicity of Cl 7-alkylated androgens (cholestasis, tumors) its use should be avoided. Orally active mesterolone is 1 a-methyl-dihydrotestosterone. Trans-dermal delivery systems for T. are also available. 

Shaw, L.A., McClements, D.J., Decker, E.A. (2007). Spray-dried multilayered emulsions as a delivery method for co-3 fatty acids into food systems. Journal of Agricultural and Food Chemistry, 55, 3112-3119. 

Unlike fatty acids, cholesterol is not degraded to yield energy. Instead excess cholesterol is removed from tissues by HDL for delivery to the liver from which it is excreted in the form of bile salts into the intestine. The transfer of cholesterol from extrahepatic tissues to the liver is called reverse cholesterol transport. When HDL is secreted into the plasma from the liver, it has a discoidal shape and is almost devoid of cholesteryl ester. These newly formed HDL particles are good acceptors for cholesterol in the plasma membranes of cells and are converted into spherical particles by the accumulation of cholesteryl ester. The cholesteryl ester is derived from a reaction between cholesterol and phosphatidylcholine on the surface of the HDL particle catalyzed by lecithimcholesterol acyltransferase (LCAT) (fig. 20.17). LCAT is associated with FIDL in plasma and is activated by apoprotein A-I, a component of HDL (see table 20.3). Associated with the LCAT-HDL complex is cholesteryl ester transfer protein, which catalyzes the transfer of cholesteryl esters from HDL to VLDL or LDL. In the steady state, cholesteryl esters that are synthesized by LCAT are transferred to LDL and VLDL and are catabolized as noted earlier. The HDL particles themselves turn over, but how they are degraded is not firmly established. 

Their mode of appearance in the lumen of the intestine is rather complicated and involves activation of trypsinogen secretion by enterokinase. Once trypsin is formed it activates chymotrypsinogen. Pancreatic lipase is also secreted into the lumen with the pancreatic fluid. The digestion process of fatty acids by their lipase-mediated hydrolysis is completed by bile salts, which are also secreted in the duodenum and are crucial for micellization of lipophilic compounds. The micelles formed in the duodenum enable the absorption of hydro-phobic drugs such as steroids. They pose, however, a serious constraint for the stability of drug delivery carriers such as liposomes and emulsions. 

Beside the bile salts, the anionic surfactants investigated for enhanced intestinal delivery were mainly sodium salts of fatty acids and their derivatives. These include sodium salts of saturated and unsaturated fatty acids (C8-Ci8), SLS, dioctyl sodium sulfossuccinate (DOSS), and others. 

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