Biomembrane permeability

PS Burton, RA Conradi, NFH Ho, AR Hilgers, RT Borchard. How structure features influence the biomembrane permeability of peptides. J Pharm Sci 85 1336-1340,... 

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). 

Liao H, Wang JH (2005) Biomembrane-permeable and ribonuclease-resistant siRNA with enhanced activity. Oligonucleotides 15(3) 196-205... 

Bemkop-Schnilrch A, Qausen AE Biomembrane permeability of peptides Strategies to improve their mucosal uptake. Mini Rev Med Chem 2002, 2, 295-305. 

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 ... 

It was postulated that the aqueous pores are available to all molecular species, both ionic and non-ionic, while the lipoidal pathway is accessible only to un-ionised species. In addition, Ho and co-workers introduced the concept of the aqueous boundary layer (ABL) [9, 10], The ABL is considered a stagnant water layer adjacent to the apical membrane surface that is created by incomplete mixing of luminal contents near the intestinal cell surface. The influence of drug structure on permeability in these domains will be different for example ABL permeability (Paq) is inversely related to solute size, whereas membrane permeability (Pm) is dependent on both size and charge. Using this model, the apparent permeability coefficient (Papp) through the biomembrane may therefore be expressed as a function of the resistance of the ABL and... 

Hamalainen KM, Kontturi K, Auriola S, Murtomaki L, Urtti A. Estimation of pore size and pore density of biomembranes from permeability measurements of polyethylene glycols using an effusion-like approach. J Control Release 49 97-104 (1997). 

Central to the osmosis phenomenon is the semipermeable membrane (SPM), whose physical properties and species-selectivity directly govern the kinetics and thermodynamics of osmotic flow. Naturally occurring biomembranes of high selectivity, permeable to water but not to other solutes, are ubiquitous, for example, in macroscopic stomach linings and blood vessels, as well as in the microscopic cell membranes that encapsulate all known cell types. Some common synthetic membranes, such as Gore-Tex and cellophane, also exhibit selective permeability and osmotic activity. 

In this case, a stationary-state coupling occurs between the flow of component O and the reaction. The coupling is generally a property of the membrane, and is associated with enzymes that are an integral part of the membrane. Table 10.1 shows the permeability and reflection coefficients for some biomembranes. 

There can be no doubt that one of the most interesting applications of the results from studies of bilayers is to biomembranes and other biostructures, Investigations of the stability and permeability of biomembranes are particularly of great interest. For instance, it is known [425-427] that a possible mechanism of the transfer of permeant (e.g. water dissolved ions, etc.) across a bilayer biomembrane is the passage of the permeant through microholes in the membrane. The statistically distributed holes in the bilayer biomembrane, formed by the mechanism of nucleation described, may thus turn out to be very important for the permeability of such biomembranes. 

When two electrolyte solutions at different concentrations are separated by an ion--permeable membrane, a potential difference is generally established between the two solutions. This potential difference, known as membrane potential, plays an important role in electrochemical phenomena observed in various biomembrane systems. In the stationary state, the membrane potential arises from both the diffusion potential [1,2] and the membrane boundary potential [3-6]. To calculate the membrane potential, one must simultaneously solve the Nernst-Planck equation and the Poisson equation. Analytic formulas for the membrane potential can be derived only if the electric held within the membrane is assumed to be constant [1,2]. In this chapter, we remove this constant held assumption and numerically solve the above-mentioned nonlinear equations to calculate the membrane potential [7]. 

Fabaceae and Plantaginaceae. When dissolved in water, saponins form soapy solutions and can therefore be used as detergents in the preparation of galenicals and cosmetics. Saponins can increase the permeability of biomembranes and may thus exhibit cytotoxic, haemolytic and antiviral properties most of them are highly toxic for fish. Moreover, steroid saponins are important starting materials for the commercial production of steroid hormones. 

The action of "holothurin" on the membrane potential and conductivity of giant squid axon membrane was studied by De Groof Narahashi [85]. The action of holothurin on the outside of the intact axon at a concentration of 2x10 M caused irreversible membrane depolarization, while the membrane potential approached zero. Elimination of Na from outer side of membrane or from both sides led to partial depolarization. A possible mechanism, based on the biomembrane depolarization by glycosides, was proposed to be connected with the increasing membrane permeability for Na ions. 

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