Transport hydrophilic substances

Under certain conditions, the transfer of various molecules across the membrane is relatively easy. The membrane must contain a suitable transport mediator , and the process is then termed facilitated membrane transport . Transport mediators permit the transported hydrophilic substance to overcome the hydrophobic regions in the membrane. For example, the transport of glucose into the red blood cells has an activation energy of only 16 kJ mol-1—close to simple diffusion. 

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. 

Molecular size. For hydrophilic substances, as molecular weight and molecular size and radius increase, permeability typically diminishes. Small molecular weight perme-ants (MW < 100 Da) are rapidly transported through the buccal mucosa. 

The inner mitochondrial membrane is impermeable to most charged or hydrophilic substances. However, it contains numerous transport proteins that permit passage of specific molecules from the cytosol (or more correctly, the intermembrane space) to the mitochondrial matrix. 

Other drug-delivery systems may include double emulsions, usually W/O/W, for transporting hydrophilic dmgs such as vaccines, vitamins, enzymes, hormones [441], The multiple emulsion also allows for slow release of the delivered drug and the time-release mechanism can be varied by adjusting the emulsion stability. Conversely, in detoxification (overdose) treatments, the active substance migrates from the outside to the inner phase. 

A number of workers have observed amino acids in lipide extracts, including those of microbial origin (11, 12, 17, 29). Recently, Macfar-lane (34) has reported that most of the phospholipide in Clostridium welchii is bound to amino acids and that some of this material occurs as the O-amino acid ester of phosphatidylglycerol. The relatively prominent occurrence of lipides in cell membranes has led to the recurrent suggestion that transport of hydrophilic substances through such membranes would be greatly facilitated by combination with hydrophobic substances. Consequently, most workers who have observed the incorporation of amino acids into lipide fractions quite naturally... 

Since biological membranes act as barriers for hydrophilic and large molecules, a mobile carrier molecule, due to increased mobility of the substrate-carrier complex, may increase the transport of a substrate. Facilitated transport may be described by the jumping mechanism for a fast reaction between the carrier and substrate. Consider a schematic of facilitated transport shown in Figure 9.8. If the transport of substance-carrier across the membrane is not fast enough, then the conventional diffusion-reaction system of Eq. (9.180) is described by... 

Brain vascular endothelial cells are linked by tight junction proteins creating high-resistance junctions between cells that effectively prevent the movement of hydrophilic substances, including electrolytes, such as Na and K+. Water moves across the lipid bilayer of endothelial cells through simple diffusion and vesicular transport (Tait et al., 2008). However, specialized water channels are formed by molecules called aquaporins (AQPs), which are highly expressed in blood-brain interfaces to facilitate the transport of water across cell membranes. 

The dominant path of distribution and elimination in the vitreous depends on a molecule s physicochemical properties and its substrate affinity. Lipophilic compounds, such as fluorescein (250) or dexamethasone (251), and compounds subject to active transport mechanisms, tend to be eliminated via the retina (Fig. 16). On the other hand, hydrophilic substances, such as fluorescein glucuronide, and compounds with poor retinal permeability, such as fluorescein dextran, tend to exit the vitreous anteriorly through the hyaloid membrane into the posterior chamber and subsequently into the anterior chamber, where they are subject to elimination pathways for aqueous humor (250). In general, shorter vitreal half-lives are associated with elimination through the retina, with its high surface area, whereas longer half-lives are indicative of elimination through the hyaloid membrane. 

Many substances cross biological membranes according to their lipid solubility. Other polar molecules, such as amino acids and glucose, cross the membranes more rapidly than expected according to their solubUity in lipids. Cations, such as Na" and K, also cross membranes rapidly in spite of their hydrophilic nature. This passive transport of substances at higher rates than predicted from their lipid solubility is termed facilitated diffusion. That proteins are directly involved in facilitated diffusion was shown by comparison of experiments with natural membranes and synthetic membranes produced with phospholipid films. With phospholipid films all molecules, except water, diffuse according to lipid solubility and molecular size. Ions are essentially impermeable. The addition of membrane proteins, however, frequently allowed many polar and charged species to penetrate the membrane at rates comparable to natural membranes. 

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."- ... 

Core-multishell architectures (CMS) have been developed based on hyper-branched polymers, such as poly(ethylene imine) (PEI) and PG with an amphiphilic alkyl-PEG shell. These CMS nanocarriers can encapsulate a wide range of hydrophobic and hydrophilic substances that can be transported in both organic solvents and aqueous systems [36, 37] (Eig. 6.15). 

Wertz and Downing 1991), which renders the corn-eocyte surface hydrophobic in character. Between the lipid bilayers, thin water sheets provide a continuum, allowing transport of hydrophilic substances in the plane of the bilayer (Fig. 2b). In a corresponding manner, hydrophobic substances are able to diffuse in the plane of the bilayers and, thus, the intercorneocyte space enables both hydrophilic and hydrophobic substance transport (Engstrom et al. 1995). Transport normal to the bilayer structures is necessary for penetration, and this will be dealt with below. 

Recently, a three-dimensional molecular assembly model was proposed by the author, using the complete amino acid sequence of the lipoprotein. As will be discussed, this assembly model describes lipoprotein complexes as tubular, hydrophilic channels through the outer membrane, which serve as passive diffusion pores. Thus, the lipoprotein serves an important function for transport of substances required for growth. 

Either the transport mediators bind the transported substances into their interior in a manner preventing them from contact with the hydrophobic interior of the membrane or they modify the interior of the membrane so that it becomes accessible for the hydrophilic particles. 

Most hydrophilic, or water-soluble, substances are repelled by this hydrophobic interior and cannot simply diffuse through the membrane. Instead, these substances must cross the membrane using specialized transport mechanisms. Examples of lipid-insoluble substances that require such mechanisms include nutrient molecules, such as glucose and amino acids, and all species of ions (Na+, Ca++, H+, Cl, and HC03). Therefore, the plasma membrane plays a very important role in determining the composition of the intracellular fluid by selectively permitting substances to move in and out of the cell. 

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]. 

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