Biological membranes solubility parameters

The physico-chemical properties may provide indications about the absorption of the substance for various routes of exposure and may therefore be of importance in the evaluation whether an appropriate administration route has been applied in the available experimental toxicity studies. In order for a substance to be absorbed, it must cross biological membranes. Most substances cross biological membranes by passive diffusion. This process requires a substance to be soluble both in lipid and water. The most useful parameters providing information on the potential for a substance to diffuse across biological membranes are the logPoctanoi/water and the water solubility. 

In order for a substance to be absorbed, it must cross biological membranes. Most substances cross by passive diffusion. This process requires a substance to be soluble both in lipid and water. The most useful parameters providing information on the potential for a substance to diffuse across biological membranes are the octanol/water partition coefficient (Log P) value and the water solubility. The Log value provides information on the relative solubility of the substance in water and the hydrophobic solvent octanol (used as a surrogate for lipid) and is a measure of lipophilicity. Log P values above zero indicate that the substance is more soluble in octanol than water, i.e., is lipophilic, and values below zero (negative values) indicate that the substance is more soluble in water than octanol, i.e., is hydrophilic. In general, moderate Log P values (between 0 and 4) are favorable for absorption. However, a substance with a Log P value around 0 and low water solubility (around 1 mg/1) will also be poorly soluble in lipids and hence not readily absorbed. It is therefore important to consider both the water solubility of a substance and its Log P value when assessing the potential of that substance to be absorbed. 

On entering the stomach an oral dose must first dissolve in the aqueous environment, prior to being absorbed across the walls of the gastrointestinal tract. The rate and extent of dissolution is therefore an important parameter. Solubility issues are discussed elsewhere in this book (see Chapter 4), but it is important to note that any new drug must possess the correct balance between aqueous solubility, allowing it to dissolve in the stomach and lipophilicity, to permit transfer across biological membranes. Poor solubility can result in a low oral bioavailability, although this problem may be resolved in some instances by judicious choice of formulation. 

The choice of n-octanol is based on its ability to mimic the lipophilicity of the biological membranes [33] and further its solubility parameter (8 = 10.24 solubility... 

Other parameters that are informative for the biological activity of molecules (solubility, volatility, lipophilicity, membrane permeability, stability in biological fluids, kinetic parameters, etc.), can, in principle, also be... 

The above mentioned observation prompted some authors to further analyze both theoretically and experimentally the parameters governing the concentration of the subtrates in the vicinity of the enzyme. Whereas the water-soluble substrates (malonyl-CoA, NADPH-NADH) did not exhibit unexpected properties, it was observed that not only the acyl-CoA partitions between water and the biological membranes (as had been known for years), but that, unexpectedly, the partition coefficient seemed to vary as a function of the surface density (4). More surprising was the observation that the partition of a given amount of acyl-CoA between water and a given amount of membranes was independent of the water volume, i.e. was in marked contrast to the definition itself of a partition coefficient which involves the ratios of concentrations of a given amphiphilic molecule in membrane and in water (5). 

The relationship between chemical structure, lipophilicity and its disposition in vivo has been reviewed by a number of authors (e.g., Koehler et al. 1988). It has been shown that many biological phenomena can be correlated with this parameter, such that quantitative structure activity relationships (QSARs) maybe deduced. These include solubility, absorption potential, membrane permeability, plasma protein binding, volume of distribution and renal and hepatic clearance. 

As biological systems have always been an inspiration for scientists, intracellular compartments (such as lysosomes or mitochondria) also have their artificial equivalents in polymer vesicles, called polymersomes. Polymersomes are spherical compartments with a bi- or monolayer membrane, generated by self-assembly of di- or triamphiphilic block copolymers in diluted aqueous conditions. To favor the formation of structures such as polymersomes, it is necessary to have a hydrophilic fraction of the copolymer mass of 25-40%, and polymer concentration above the critical micellar concentration. Other parameters that affect the self-assembly process, and therefore the final architecture of the polymer supramolecular assemblies, are the molecular weight of the copolymer (Af ), block lengths, solubility, and glass transition temperature (Tg) [21,22], The relative mass or volume fraction of each block is a key parameter in the formation of a self-assembled structure with a certain membrane curvature, and ultimately, with a specific architecture. The of the copolymer (and thus the block lengths) dictates the membrane thickness and polymersome properties, such as membrane fluidity, stabihty, and permeabihty [21,74],... 

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