Membranes physicochemical characteristics

The extent of absorption and rate of transport are important properties of a membrane. Physicochemical characteristics such as electrical conductivity and ion selectivity are closely related to the amount of water sorption. On the other hand, mass transport in solutions next to membranes depends on the buildup of the hydrodynamic boundary layers, especially at high current densities. Therefore, the maximum current density is determined by the diffusion of chemical species through the boundary layers outside the membrane and not so much by processes that occur inside the membrane. The limiting current density, therefore, is not strongly affected by the water content of the membrane or by the processes of water transport through it. 

Figure 3 shows a steady diffusion across a membrane. As in the previous case, the membrane separates two well-mixed dilute solutions, and the diffusion coefficient Dm is assumed constant. However, unlike the film, the membrane has different physicochemical characteristics than the solvent. As a result, the diffusing solute molecules may preferentially partition into the membrane or the solvent. As before, applying Fick s second law to diffusion across a membrane, we... 

Too often results are compromised by a poor experimental set-up of the studies and nontransparent data. Even essential information such as the relevant physicochemical characteristics of the drug in relation to the chosen aerosol system or the fraction that is deposited in the alveoli is often not provided. This makes it impossible to evaluate the impact of such studies. As a result, it is unclear until now to what extent and at what rate macromolecular drugs (> 20 kDa) can be absorbed by the lung. Moreover, the routes by which macromolecules pass through the different pulmonary membranes, especially the alveolar membrane, are unknown. Appropriate experiments and models that provide adequate answers to these questions are required in the coming years. 

Absorption is described by determining the rate constant of drug passing into the bloodstream at successive time intervals after administration. Residues may be found in tissues after some or all of the drug has been systemically absorbed. Absorption is influenced by the properties of cell membranes, the physicochemical characteristics of the drug, and the route of drug administration (1). 

Apart from the properties of the cell membranes, certain physicochemical characteristics of the drugs can significantly influence the rate of their absorption. Most drugs are either weak acids or bases that exist in solution as a mixture of ionized and nonionized forms. Nonionized forms are more lipophilic whereas ionized forms more hydrophilic. Consequently, the nonionized forma are lipid soluble and able to permeate rapidly across cell membranes. This process is known as passive nonionic diffusion. 

Perhaps the most important feature of the plasma membrane is that it is selectively permeable. Overall permeability of the membrane to a chemical depends on the nature of the membrane, its surface charge and rigidity, and the chemical in question. Therefore, only certain substances are able to pass through the membrane, depending on particular physicochemical characteristics. It will be apparent throughout this book that the physicochemical characteristics of molecules are major determinants of their disposition and often of their toxicity. 

Thus, with regard to the passage of foreign, potentially toxic molecules through membranes, the following physicochemical characteristics are important ... 

The concentration gradient. This is normally in the direction external to internal relative to the cell or organism. The rate of diffusion is affected by certain factors it is proportional to the concentration gradient across the membrane the area and thickness of the membrane and a diffusion constant, which depends on the physicochemical characteristics of the compound in question. This relationship is known as Fick s Law ... 

Absorption is necessary for the chemical to exert a systemic biological/toxic effect and involves crossing membranes. Membranes are semipermeable phospholipid/protein bilayers. The phospholipids and proteins are of variable structure, and the membrane is selectively permeable. The physicochemical characteristics of foreign molecules that are important include size/shape, lipid solubility, structure, and charge/polarity. 

Dermal and transdermal delivery requires efficient penetration of compounds through the skin barrier, the bilayer domains of intercellular lipid matrices, and keratin bundles in the stratum corneum (SC). Lipid vesicular systems are a recognized mode of enhanced delivery of drugs into and through the skin. However, it is noteworthy that not every lipid vesicular system has the adequate characteristics to enhance skin membrane permeation. Specially designed lipid vesicles in contrast to classic liposomal compositions could achieve this goal. This chapter describes the structure, main physicochemical characteristics, and mechanism of action of prominent vesicular carriers in this field and reviews reported data on their enhanced delivery performance. 

Iontophoresis by definition is the process of transport of ions into or through a tissue by the use of an applied potential difference across the tissue [52], Depending on the physicochemical characteristics of a molecular species, electrorepulsion is usually the primary mechanism of transdermal transport for ions, whereas electroosmosis and increased passive diffusion (as a result of the reduced barrier properties) are more prominent for neutral species [53]. In contrast, enhancement in flux for neutral or weakly charged species during electroporation arises predominantly from the reduced barrier properties of the membrane, whereas direct electrorepulsion is usually of secondary importance [25],... 

Complexes of intrinsic membrane proteins and lipids can form hydrophilic or hydro-phobic channels that allow transport of molecules with different physicochemical characteristics. The amphipathic nature of the membrane creates a barrier for ionized, highly polar drugs, although it does not completely exclude them. The presence of pores of approximately 4 A are believed to allow for ready movement of small molecules such as water. Thus certain molecules that ordinarily would be excluded can rapidly traverse the highly lipid membrane barrier. 

Desferrioxamine (DFO) is a trihydroaminic acid obtained from isolates of Streptomyces pilosus. Since 1963 it has been clinically used as an iron-chelating agent in patients with iron overload [261], DFO effectively chelates trivalent ions such as iron and Al, producing respectively ferrioxamine and aluminox-amine [12, 30, 260-269]. DFO displays rather complicated physicochemical characteristics. Unchelated DFO is a straight chained lipophilic molecule that can penetrate plasma membranes and undergo metabolic breakdown. In contact with Al, it twines itself around the metal to form stable hydrophilic... 

Various experimental techniques have demonstrated that cell membranes have a large lipid component, and most drugs cross such membranes by simple passive diffusion. In order to cross these lipid membranes, a drug should be in the lipid-soluble or un-ionized form and also be in solution. The various physicochemical characteristics of the drug are, therefore, of paramount importance as far as drug penetration across the oral mucosa is concerned. 

Introduced in 1943, ED remains the most frequently used procedure. A membrane separates two compartments, and at equilibrium, one compartment contains the plasma or serum with protein and bound ligand, whereas free drug is sequestered to the buffer solution compartment. The unbound fraction is determined by the ratio of drug concentration on the buffer side [D] divided by that in the plasma P] -I- PP]. Results are influenced by drug properties, proteins (content and concentration), volume of compartments, buffer strength, and ionic composition as well as by the thickness and physicochemical characteristics of the membrane. Time and temperature are major environmental factors, and dialysis for 4h (or less) at 37°C has been found optimal for acidic and basic drugs. ... 

Synthetic phospholipids are commercially available and they contain polar heads occurring in nature and and the same type of fatty acid in both, 9 -l and sn-2 sites. The acyl chains may be mainly myristoyl (C14 0), palmitoyl (C16 0), olcoyl (C16 l) or stearoyl (C18 0) residues. The physicochemical characteristics of the lipidic bilayers that are prepared from synthetic phospholipids are well defined. The lipid composition influences many physical properties of model membranes and it has been shown that single synthetic lipids or mixtures of short and long fatty acid chains can produce stable lipidic bilayers and liposomes. 

The most important phase for the membranes of living cells is the lamellar fluid pliase, In this phase, the conformational order of the fatty acid chains is low and the lipid lateral mobility is substantial. The lempcrature at which the liquid crystal phase alters to gel phase and, as a result, the fatty acid chains obtain a high degree of conformational order with low mobility, is called the main transition temperature (Tm). This temperature is considered as an important physicochemical characteristic at isobaric conditions, indicating that the system exists in equilibrium and the AG at the Tm point is zero (AG=0). 

Liposomes belong to the class of lyotropic liquid crystals. Obviously, their physicochemical characteristics and their biocompatibility with cell membranes has given them several advantages they can dissolve, protect and deliver hydrophobic and hydrophilic molecules. Several applications of liposomes relate to a broad range of sciences and disciplines such as, biochemistry, chemistry, biology, medicine, biophysics, physics and mathematics. 

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