Transport lipophilic substances

The production of microemulsions is comparatively simple and cost-effective, and thus, they have attracted a great interest as drug-delivery vehicles. Microemulsions have the capability of transporting lipophilic substances through an aqueous medium, and can also carry hydrophilic substances across lipoidal medium. Based on this attribute, potential of microemulsions has been explored for oral, transdermal, parenteral, topical, and pulmonary administration of lipophilic and hydrophilic drugs. In the last decade, microemulsions have also been explored for their potential as vehicles for topical ocular drug delivery."- ... 

Although the absence of paracellular transport across the BBB impedes the entry of small hydrophilic compounds into the brain, low-molecular-weight lipophilic substances may pass through the endothelial cell membranes and cytosol by passive diffusion [7]. While this physical barrier cannot protect the brain against chemicals, the metabolic barrier formed by the enzymes from the endothelial cell cytosol may transform these chemicals. Compounds transported through the BBB by carrier-mediated systems may also be metabolized. Thus, l-DOPA is transported through the BBB and then decarboxylated to dopamine by the aromatic amino acid decarboxylase [7]. 

The intercellular route is considered to be the predominantly used pathway in most cases, especially when steady-state conditions in the stratum corneum are reached. In case of intercellular absorption, substance transport occurs in the bilayer-structured, continuous, intercellular lipid domain within the stratum corneum. Although this pathway is very tortuous and therefore much longer in distance than the overall thickness of the stratum corneum, the intercellular route is considered to yield much faster absorption due to the high diffusion coefficient of most drugs within the lipid bilayer. Resulting from the bilayer structure, the intercellular pathway provides hydrophilic and lipophilic regions, allowing more hydrophilic substances to use the hydrophilic and more lipophilic substances to use the lipophilic route. In addition, it is possible to influence this pathway by certain excipients in the formulation. 

Ionophores (ion carriers) are lipophilic substances, capable of binding and carrying specific cations through the biological membranes. They differ from the uncouplers in that they promote the transport of cations other than H+ through the membrane. 

Bilirubin - an apolar, water-insoluble lipophile substance - is potentially toxic. It is bound to serum albumin and transported to the sinusoidal membrane of the liver cell as a bilirubin-albumin complex, (s. fig. 3.1) The binding capacity of albumin is exceeded only at a serum bilirubin concentration of >4—5 mg/dl. In the case of decreased albumin binding (e. g. in acidosis) or oversaturated binding capacity, there is a danger of toxic cell damage due to the diffusion of unbound bilirubin into the cells (in some cases accompanied by kernicterus). Neonates and premature babies are at particular risk because of their immature blood-cerebrospinal fluid barrier. Albumin-bound bilirubin can function as an antioxidant to intercept free radicals and/or O2 radicals. (93) (s. tab. 3.25)... 

The first part of Chapter 1 contains a brief review of the chemistry and biochemistry backgroimd required to understand many of the topics covered in this book. For example, the biochemical apparatus used for the digestion and transport of a specific nutrient depends on whether the nutrient is fat soluble or water soluble. Although the actual solubility of a nutrient in water is controlled by its chemical groups, the effective solubility of lipophilic substances can be increased by incorporation in micelles. Similarly, the ionization of water-soluble nutrients in the body can change depending on the surrounding environment. 

Lindane is a less lipophilic substance in comparison with many other serious envirotoxicants but still is characterized by a high degree of bioavailability. Furthermore, the substance is rather persistent, volatile and subject to longdistance transport. It bioaccumulates to a pronounced degree in lower biota and fish, although mammals and birds biotransform and excrete the metabolites to a great extent. Thus, the levels of lindane in contrast to, for example, PCBs have... 

The endothelial cells actively, as well as passively, serve to protect the brain. Because they contain a variety of drug-metabolizing enzyme systems similar to the drug-metabolizing enzymes found in the liver, the endothelial cells can metabolize neurotransmitters and toxic chemicals and, therefore, form an enzymatic barrier to entry of these potentially harmful substances into the brain. They actively pump hydrophobic molecules that diffuse into endothelial cells back into the blood (especially xenobiotics) with P-glycoproteins, which act as transmembranous, ATP-dependent efflux pumps. Although lipophilic substances, water, oxygen, and carbon dioxide can readily cross the blood-brain barrier by passive diffusion, other molecules depend on specific transport systems. Differential transporters on the luminal and abluminal endothelial membranes can transport compounds into, as well as out of, the brain. 

Endothelial cells lining the inside of blood vessels play an important role in the transport of materials to the intercellular fluid outside the blood vessels. Hydrophobic (water insoluble) materials can pass directly through the lipoprotein double layer of the endothelial cell membranes, so the entire cell surface is available for transport. Lipophilic (soluble in fats or lipids) Oj is one of these substances. 

The transport flux for lipophilic substances through an o/w microemulsion has been shown by Xenakis and Tondre [139] in the light of reasonings of Ward [149] and Cussler [150] to be... 

Passive transport of lipophilic substances may occur via the fluid bilayer membrane of the cells lining the membranes. This transcellular route is the most important route for membrane passage of active substances. This transport mechanism is not only driven by the concentration gradient over the absorptive membrane, but also by the oil to water partition coefficient of the active substance (expressed as the octanol-water partition coefficient, which describes the ratio of the substance s solubility in aqueous and fatty phases, see Sect. 16.1.9). More lipophilic... 

Lipoproteins are the endogenous transport vehicles for lipids and lipophilic substances but also for therapeutic drugs as hydrophobic porphyrins in blood. Lipoproteins consist of a lipid core (triglycerides, cholesterol and cholesterol esters in different ratios in the different types of lipoproteins)... 

ABC transporters are also important at the blood-brain barrier (BBB). The BBB only allows the entry of small lipophilic substances by passive diffusion. However, the uptake of lipophilic compounds in the brain is relatively low due to the high activity of P-gp, MRP, and organic anion transporting polypeptides (OATPs). These transporters catalyse a rapid efflux of lipophilic xenobiotics from the CNS (62). In order to allow therapeutic agents to reach the CNS, inhibitors of ABC transporters are of medicinal importance. 

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