Biological membranes permeability

Triton extracts of gastric mucosa contain apparently three materials which can produce channels in lipid bilayers with conductances of 2.5 X 10 ° mho. One material is apparently neutral and cation-selective, another charged, voltage-dependent and anion-selective, whilst the third is non-selective [41]. Material which produces K -selective channels in bilayers has been extracted from excitable tissue [42]. The data obtained so far with these natural channel formers are relatively crude compared with the elegant studies with channel-fdrming antibiotics. Therefore, it is, as yet, unclear whether these materials have definitive roles in biological membrane permeability. 

Physiologically Based Phamiacokinetic (PBPK) Model—Comprised of a series of compartments representing organs or tissue groups with realistic weights and blood flows. These models require a variety of physiological information tissue volumes, blood flow rates to tissues, cardiac output, alveolar ventilation rates and, possibly membrane permeabilities. The models also utilize biochemical information such as air/blood partition coefficients, and metabolic parameters. PBPK models are also called biologically based tissue dosimetry models. 

Crowe, L.M. Crowe, J.H. (1986). Hydration-dependent phase transitions and permeability properties of biological membranes. In Membranes, Metabolism and Dry Organisms, ed. A.C. Leopold, pp. 210-30. Ithaca, N.Y. Comstock Publishing Associates. 

In the 1940s a number of phenomena were discovered which do not fit these ideas. It was shown in particular that biological membranes are permeable, not only... 

Absorption across biological membranes is often necessary for a chemical to manifest toxicity. In many cases several membranes need to be crossed and the structure of both the chemical and the membrane need to be evaluated in the process. The major routes of absorption are ingestion, inhalation, dermal and, in the case of exposures in aquatic systems, gills. Factors that influence absorption have been reviewed recently. Methods to assess absorption include in vivo, in vitro, various cellular cultures as well as modelling approaches. Solubility and permeability are barriers to absorption and guidelines have been developed to estimate the likelihood of candidate molecules being absorbed after oral administration. ... 

The pH-partition theory or nonionic permeability hypothesis was first described by Jacobs in 1940 [66]. According to this concept, only neutral, preferably nonpolar compounds are able to cross biological membranes. The transcellular permeability pH-profile is then essentially characterized by the membrane partition coefficient and the pKa of the compound. The simplest quantitative description of membrane permeation is given by ... 

Whereas the relationship of solute permeability with lipophilicity has been studied in a large number of in vivo systems (including intestinal absorption models [54,55], blood-brain [56 58] and blood nerve [59] barrier models, and cell culture models [60 62], to name just a few), numerous in vitro model systems have been developed to overcome the complexity of working with biological membranes [63-66]. Apart from oil-water systems that are discussed here, the distribution of a solute between a water phase and liposomes is... 

It is well known that the permeabilities across biological membranes and model lipid bilayers strongly depend on both the degree of lipid chain packing in the membranes... 

With the exception of rather small polar molecules, the majority of compounds, including drugs, appear to penetrate biological membranes via a lipid route. As a result, the membrane permeability of most compounds is dependent on K0/w. The physicochemical interpretation of this general relationship is based on the atomic and molecular forces to which the solute molecules are exposed in the aqueous and lipid phases. Thus, the ability of a compound to partition from an aqueous to a lipid phase of a membrane involves the balance between solute-water and solute-membrane intermolecular forces. If the attractive forces of the solute-water interaction are greater than those of the solute-membrane interaction, membrane permeability will be relatively poor and vice versa. In examining the permeability of a homologous series of compounds... 

Up to now we have focused on measurement of permeability and membrane retention at pH 7.4. Since the GIT covers a range of pH values, with pH 5-8 characterizing the small intestine, it is necessary to address the pH dependence of the transport of drug molecules. Even nonionizable molecules may be affected by pH dependence, since several biological membrane components themselves are ionizable (pKa values listed in Fig. 7.4). For example, with PS, PA, and DA (free fatty acid) undergoing changes in charge state in the pH 5-8 interval. In this section, we examine the consequences of pH dependence. 

It has been known for some years that gramicidin forms transmembrane ion channels in lipid bilayers and biological membranes and that these channels are assembled from two molecules of the polypeptide 213). The channels are permeable specifically to small monovalent cations [such as H+, Na+, K+, Rb+, Cs+, Tl+, NH4+, CHjNHj, but not (CH3)2NH2+J and small neutral molecules (such as water, but not urea). They do not allow passage of anions or multivalent cations 21 n. 

O Kedem, A Katchalsky. Thermodynamic analysis of the permeability of biological membranes to nonelectrolytes. Biochim Biophys Acta 27 229-246, 1958. 

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