Permeability model membranes

Rourke, B.C. and Gibbs, A.G. (1999). Effects of lipid phase transitions on cuticular permeability model-membrane and in situ studies. J. Experim. Biol., 202, 3255-3262. 

Papahadjopoulos, D., and Watkins, J. C. (1967). Phospholipid model membranes. II. Permeability properties of hydrated liquid crystals, Biochim. Biophys. Acta. 135. 639-652. 

Equation (20-80) requires a mass transfer coefficient k to calculate Cu, and a relation between protein concentration and osmotic pressure. Pure water flux obtained from a plot of flux versus pressure is used to calculate membrane resistance (t ically small). The LMH/psi slope is referred to as the NWP (normal water permeability). The membrane plus fouling resistances are determined after removing the reversible polarization layer through a buffer flush. To illustrate the components of the osmotic flux model. Fig. 20-63 shows flux versus TMP curves corresponding to just the membrane in buffer (Rfouimg = 0, = 0),... 

THE CASE FOR THE IDEAL IN VITRO ARTIFICIAL MEMBRANE PERMEABILITY MODEL... 

The Ideal in vitro Artificial Membrane Permeability Model... 

K. Miyajima, S. Tanikawa, M. Asano, and K. Matsuzaki. Effects of absorption enhancers and lipid composition on drug permeability through the model membrane using stratum corneum lipids. Chem. Pharm. Bull. 42 1345-1347 (1994). 

Cell monolayers grown on permeable culture inserts form confluent mono-layers with barrier properties and can be used for drug absorption experiments. The most well-known cell line for the in vitro determination of intestinal drug permeability is the human colon adenocarcinoma Caco-2 [20, 21], The utility of the Caco-2 cell line is due to its spontaneous differentiation to enterocytes under conventional cell culture conditions upon reaching confluency on a porous membrane to resemble the intestinal epithelium. This cell model displays small intestinal carriers, brush borders, villous cell model, tight junctions, and high resistance [22], Caco-2 cells express active transport systems, brush border enzymes, and phase I and II enzymes [22-24], Permeability models... 

Sugano et al. studied the membrane permeation of 51 benzamidine-based thrombin inhibitors in a rat everted sac permeability model [197]. They reported significant membrane permeabilities in this in vitro model, which they attributed to passive paracellular transport, a different absorption mechanism to transcellular permeability. 

Membrane permeability is one of the most important determinants of pharmacokinetics, not only for oral absorption, but also for renal re-absorption, biliary excretion, skin permeation, distribution to a specific organ and so on. In addition, modification of membrane permeability by formulation is rarely successful. Therefore, membrane permeability should be optimized during the structure optimization process in drug discovery. In this chapter, we give an overview of the physiology and chemistry of the membranes, in vitro permeability models and in silica predictions. This chapter focuses on progress in recent years in intestinal and blood-brain barrier (BBB) membrane permeation. There are a number of useful reviews summarizing earlier work [1-5]. 

Kitson, N., et al. 1994. A model membrane approach to the epidermal permeability barrier. Biochemistry 33 6707. 

The jfipervap term in Equation (9.2) and Equation (9.5) can be derived in terms of /3evap, membrane permeabilities, and membrane operating conditions using the standard solution-diffusion model from Chapter 2. The membrane fluxes can be written as... 

The characteristics of membrane permeation are partition, including affinity, location, specific interaction with certain phospholipids, and diffusion kinetics. Because of the complex events involved during drug absorption in vivo, true membrane permeability modeling cannot always be expected. Therefore, many attempts have been made to develop suitable in vitro systems to study the permeation process and its dependence on membrane composition and drag physicochemical properties. 

Fig. 5.17 Permeability coefficients, P°, for doxorubicin transport across model membranes composed of different phospholipids. PC, phosphatidylcholine PE, phos-phatidylethanolamine PS, phosphatidylserine SM, sphingomyelin. (Reprinted from Fig. 3 of ref. 115 with permission from the American Chemical Society.)...

---