Lipids permeation

Since colloidal material has both hydrophilic and lipophilic properties, making it permeable across membrane surfaces, lipid permeation may be an important mechanism for metal uptake. Lipophilic metals, such as organic Hg, have been shown to be taken up by... 

Dosage Forms Lipid Excipients Table 3 Lipid permeation enhancers... 

There are a number of useful in vitro measures of permeability that can be used to assess how well a given molecule will be absorbed. One of the most simple is the permeation of molecules through artificial (hexadecane) membranes (referred to as PAMPA studies). These measure transcellular permeation through bulk diffusion in systems that avoid the complexity of active transport. With these types of assays, compounds can be ranked on the basis of lipid permeation alone this can be a useful gauge of ability to penetrate the gut intestinal wall. 

Permeation process of small molecules across lipid membranes studied by molecular dynamics simulations. J. Phys. Chem. 100 (1996) 16729-16738. 

Gel permeation ehromatography (GPC)/normal-phase HPLC was used by Brown-Thomas et al. (35) to determine fat-soluble vitamins in standard referenee material (SRM) samples of a fortified eoeonut oil (SRM 1563) and a eod liver oil (SRM 1588). The on-line GPC/normal-phase proeedure eliminated the long and laborious extraetion proeedure of isolating vitamins from the oil matrix. In faet, the GPC step permits the elimination of the lipid materials prior to the HPLC analysis. The HPLC eolumns used for the vitamin determinations were a 10 p.m polystyrene/divinylbenzene gel eolumn and a semipreparative aminoeyano eolumn, with hexane, methylene ehloride and methyl tert-butyl ether being employed as solvent. 

This review addresses the issues of the chemical and physical processes whereby inorganic anions and cations are selectively retained by or passed through cell membranes. The channel and carrier mechanisms of membranes permeation are treated by means of model systems. The models are the planar lipid bilayer for the cell membrane, Gramicidin for the channel mechanism, and Valinomycin for the carrier mechanism. 

The blood-brain barrier (BBB) forms a physiological barrier between the central nervous system and the blood circulation. It consists of glial cells and a special species of endothelial cells, which form tight junctions between each other thereby inhibiting paracellular transport. In addition, the endothelial cells of the BBB express a variety of ABC-transporters to protect the brain tissue against toxic metabolites and xenobiotics. The BBB is permeable to water, glucose, sodium chloride and non-ionised lipid-soluble molecules but large molecules such as peptides as well as many polar substances do not readily permeate the battier. 

Sugano, K., Hamada, H., Machida, M., Ushio, H. High throughput prediction of oral absorption improvement of the composition of the lipid solution used in parallel artifidal membrane permeation assay. J. Biomol. Screen. 2001, 6,189-196. 

Fig. 3.4 Permeability profiles for (a) warfarin (acid), (b) propranolol (base) and (c) morphine (ampholyte) based on a BBB PAMPA model (plON) composed of animal brain extract of lipids. The data (unpublished) were analyzed with the pCEL-X program (plON), with the refined parameters indicated in the three frames. In all three cases, there was evidence for the permeation of charged...

Lipophilicity is intuitively felt to be a key parameter in predicting and interpreting permeability and thus the number of types of lipophilicity systems under study has grown enormously over the years to increase the chances of finding good mimics of biomembrane models. However, the relationship between lipophilicity descriptors and the membrane permeation process is not clear. Membrane permeation is due to two main components the partition rate constant between the lipid leaflet and the aqueous environment and the flip-flop rate constant between the two lipid leaflets in the bilayer [13]. Since the flip-flop is supposed to be rate limiting in the permeation process, permeation is determined by the partition coefficient between the lipid and the aqueous phase (which can easily be determined by log D) and the flip-flop rate constant, which may or may not depend on lipophilicity and if it does so depend, on which lipophilicity scale should it be based ... 

Thomae, A. V., Wunderli-Allenspach, H., Kramer, S. D. Permeation of aromatic carboxylic adds across lipid bilayers the pH-partition hypothesis revisited. Biophys. J. 2005, 89,1802-1811. 

III. PERMEATION OF SMALL MOLECULES ACROSS LIPID BILAYERS ROLE OF BILAYER STRUCTURE... 

FIG. 13 A schematic illustration of the effects of the free surface area of lipid bilayer membranes on the permeation of two permeants with the same molecular volume, but different cross-sectional areas, (a) A lower free surface area, (b) A higher free surface area. 

In addition, data obtained from infrared, thermal, and fluorescence spectroscopic studies of the outermost layer of skin, stratum corneum (SC), and its components imply enhancer-improved permeation of solutes through the SC is associated with alterations involving the hydrocarbon chains of the SC lipid components. Data obtained from electron microscopy and x-ray diffraction reveals that the disordering of the lamellar packing is also an important mechanism for increased permeation of drugs induced by penetration enhancers (for a recent review, see Ref. 206). 

Figures 4.2b, 4.3b, and 4.4b are log-log speciation plots, indicating the concentrations of species in units of the total aqueous sample concentration. (Similar plots were described by Scherrer [280].) The uppermost curve in Fig. 4.2b shows the concentration of the uncharged species in octanol, as a function of pH. If only uncharged species permeate across lipid membranes, as the pH-partition hypothesis...

The UWL permeability is nearly the same for drugs of comparable size, and is characterized by the water diffusivity (Daq) of the drug divided by twice the thickness of the layer (ftaq), Pu = Aiq / (2 h.Aq), in a symmetric permeation cell [40], The unstirred water layer permeability can be determined experimentally in a number of ways based on pH dependency of effective permeability [25,509,535-538], stirring rate dependence [511-514,552,578], and transport across lipid-free microfilters [25,546],... 

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