Phospholipid membrane, permeability

B. G. Phospholipid membrane permeability of peptide nucleic acid. FEB. S. Lett. 

Effects of Surfactant on High-phospholipid Membrane Permeability and Retention... 

Simon, E.W. (1974). Phospholipids and plant membrane permeability. New Phyto-logist, 73, 377-420. 

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

Since lipophilic molecules have affinity for both the membrane lipid and the serum proteins, membrane retention is expected to decrease, by the extent of the relative lipophilicities of the drug molecules in membrane lipid versus serum proteins, and by the relative amounts of the two competitive-binding phases [see Eqs. (7.41)-(7.43)]. Generally, the serum proteins cannot extract all of the sample molecules from the phospholipid membrane phase at equilibrium. Thus, to measure permeability under sink conditions, it is still necessary to characterize the extent of membrane retention. Generally, this has been sidestepped in the reported literature. 

This book is written for the practicing pharmaceutical scientist involved in absorption-distribution-metabolism-excretion (ADME) measurements who needs to communicate with medicinal chemists persuasively, so that newly synthesized molecules will be more drug-like. ADME is all about a day in the life of a drug molecule (absorption, distribution, metabolism, and excretion). Specifically, this book attempts to describe the state of the art in measurement of ionization constants (p Ka), oil-water partition coefficients (log PI log D), solubility, and permeability (artificial phospholipid membrane barriers). Permeability is covered in considerable detail, based on a newly developed methodology known as parallel artificial membrane permeability assay (PAMPA). 

Fig. 10.7 RNA synthesis in vesicles. Membrane permeability can be regulated by choosing the correct chain length of the fatty acids in the phospholipids. Short chains (a) make the bilayer so unstable that even large molecules such as proteases can enter the vesicle interior and damage the polymerase. Carbon chains which are too long (b) prevent the entry of substrate molecules such as ADR RNA polymerisation in the vesicle occurs only with C14 fatty acids (c)...

Papahadjopoulos D, Nir S, Oki S. Permeability properties of phospholipid membranes effect of cholesterol and temperature. Biochim Biophys Acta 1972 ... 

Membrane permeability is another important parameter for drugs, because it is related to intestinal absorption and brain penetration. Lipophilicity is also useful in predicting these phenomena. In addition, liposome with phospholipid would be more reliable for measuring biomembrane permeability. Recently, some groups reported an EKC approach with phospholipid vesicles (56-58). 

Mecfianism of Action An antifungai that binds with phospholipids in fungal cell membrane. The altered cell membrane permeability. Therapeutic Effect Inhibits yeast growth. 

Similarly comb-like copolymers of vinyl pyrollidone and vinyl alkyl amines were shown [446] to influence the permeability of negatively charged phospholipid liposomes containing encapsulated carboxyfluorescein. At a pH of approximately 7, the copolymers allowed permeability and solute release due to polymer/liposome complex formation and disruption of the phospholipid membrane. 

As indicated in my report, we now know the rates of lateral diffusion of phospholipids in lipid bilayers in the fluid state, and in a few cases the rates of lateral diffusion of proteins in fluid lipids are also known. At the present time nothing is known about the rates of lateral diffusion of phospholipids in the crystalline, solid phases of the substances. As mentioned in my report, there are reasons to suspect that the rates of lateral diffusion of phospholipids in the solid solution crystalline phases of binary mixtures of phospholipids may be appreciable on the experimental time scale. Professor Ubbelohde may well be correct in pointing out the possibility of diffusion caused by defects. However, such defects, if present, apparently do not lead to significant loss of the membrane permeability barrier, except at domain boundaries. 

Phospholipids, components of every cell membrane, are active determinants of membrane permeability. They are sources of energy, components of certain enzyme systems, and involved in lipid transport in plasma. Because of their polar nature, phospholipids can act as emulsifying agents. The structure of most phospholipids resembles that of triglycerides except that one fatty acid radical has been replaced by a radical derived limn phosphoric acid and a nitrogen base. c.g.. choline or serine. 

When incorporated into the phospholipid membrane of liposomes, compounds 114 and 115 increased the permeability to Na+ and Li+ ions, and ion transfer proceeded by a cation-cation antiport mechanism (Figure 25) [8.208]. 

Papahadjopoulos, D., Cowden, M., and Kimelberg, H. (1973a). Role of cholesterol in membranes. Effects of phospholipid-protein interactions, membrane permeability and enzymatic adBiotjhim. Biophys. 

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