Drug delivery kidney-selective

Here, we use intestine-selective and kidney-selective drug delivery to illustrate the targeting of constitutionally expressed peptidases. 

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... 

Folate (vitamin Bg) is a low-molecular-weight (441 Da) compound essential in cell proliferation and for the biosynthesis of methionine, serine, deoxythymine add, and purine. Folate is internalized via two independent pathways either by transport of folate by the folate reeeptor or as 5-methyl-tetrahydrofolate by the reduced folate carrier. The expression of folate receptor (FR) in healthy tissue is limited to activated macrophages, placental cells, and the apical surface of polarized epithelia, where it is present in different isoforms [56]. The overexpression of FR on a broad range of solid tumors (ovary, lung, breast, kidney, brain, endometrium, and colon) makes it a suitable target for selective tumor drug delivery (for review, see [57J). 

Early assessment of the ability of a drug candidate to penetrate the CNS is critical during the drug discovery selection process, especially for therapeutic indications that require delivery to a CNS site of action. Equally important is the ability to design drugs for non-CNS indications that have minimal brain penetration to avoid undesirable CNS side effects. In vitro BBB models using primary and immortalized brain capillary endothelial cells are described in the previous sections. The Ma-dine Darby canine kidney (MDCK) cell-line is increasingly used as a substitute for the more labor-intensive in vitro BBB models in passive permeability and membrane transport studies. 

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