Blood cell culture model

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... 

A cell culture model of the blood-brain barrier. J Cell Biol 115 1725— 1735... 

The use of in vitro cell culture models for mechanistic studies and as permeability screens for the blood-brain barrier in the pharmaceutical Industry-Background and current status in the drug discovery process. Vascular Pharmacology, 38, 355-364. 

Lehr, CM., Bur, M., and Schaefer, U.F. (2006) Cell culture models of the air-blood barrier for the evaluation of aerosol medicines. ALTEX 23 Suppl, 259-64. 

Liposomal ATP protected human endothelial cells from energy failure in a cell culture model of sepsis (21). ATP-L increased the number of ischemic episodes tolerated before electrical silence and brain death in the rat (22,23). In a hypovolemic shock-reperfusion model in rats, the administration of ATP-L increased hepatic blood flow during shock and reperfusion of the liver (24). The addition of the ATP-L during cold storage preservation of rat liver improved its energy state and metabolism (25,26). Co-incubation of ATP-L with sperm cells improved their motility (27). Finally, biodistribution studies demonstrated significant accumulation of ATP-L in ischemia-damaged canine myocardium (28). 

The blood-retinal epithelial barrier and cell culture models... 

The purpose of this chapter is to present overviews of a selection of the major endothelial and epithelial barriers to drug delivery for which there are either primary culture or cell line systems that recapitulate the characteristics of the in vivo barrier. Our objective is to define some general characteristics of cell culture models and highlight the more commonly applied primary cell cultures and cell lines in use today. Specifically, we focus on cell culture models for the intestinal epithelium, blood-brain barrier, pulmonary and nasal epithelium, ocular epithelium, placental barrier, and renal epithelium. Renal epithelium was included here primarily because some cell lines derived from this tissue [e.g., Madin-Darby canine kidney cells (MDCK)] are often used as surrogates for other barriers by pharmaceutical scientists. We have arbitrarily chosen to exclude the skin and liver from the scope of this overview. However, it should be noted that hepatocyte cell culture models, for example, are becoming more widely available and have been the subject of recent reviews.1,2... 

The Blood-Retinal Epithelial Barrier and Cell Culture Models... 

The pH in the cellular interstitial space and blood compartment is known to be about 7.4. The pH present in the G1 tract will not only have an impact on the ionization of drugs, and thus on their partitioning capacity, but it will also affect the pH-dependent functionality of various carriers located in the intestinal mucosa (Tsuji and Tamai, 1996). Many of these carriers are also expressed and functionally active in the Caco-2 cell culture model (Hidalgo and Li, 1996 Ogi-hara et al., 1999 Friedrichsen et al., 2002 Putman et al., 2002a,b). Therefore, the pH of the apical medium can have a critical effect on ionization and transport of drugs, ft has for instance been shown that the absorption of w eak bases, like beta-blockers, are absorbed better in the ileum region, where the pH is around... 

Miller DW, KL Audus, RT Borchardt. (1992). Cultured bovine brain microvessel endothelial cells A model of the blood brain barrier. J Tiss Cult Meth 14 217-224. 

Primary cultures developed from pig and cow tissue are the best studied [29-32]. These models closely resemble the BBB, exhibiting many of the key biological properties. However isolation of blood-brain endothelial cells requires relatively complex cell isolation procedures which are labor-intensive and not ideal for screening purposes. Other cell types have been shown or proposed to induce barrier function, for example, astrocytes/pericytes. Significant improvements in barrier function was achieved in these primary culture models by including astrocyte conditioned media or co-culturing with astrocytes [33]. The complexity of primary cultures led to the use of epithelial cell lines not derived from the BBB (e.g., MDCK, MDCK-MDRl or LLC-PKl) [33]. 

Garlic has been reported to have lipid- and blood-pressure-lowering properties, as well as antiplatelet, antioxidant, and fibrinolytic effects. In animal models and human cell cultures, it has been shown to have antiatherosclerotic activity (see Chapter 50). The sulfur-containing component, allicin, is considered to be the principal active ingredient of garlic, but several other bioactive ingredients have also been isolated. 

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