Drug delivery intestine-selective

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

The potential for orally administered drugs to enter the intestinal lymphatics is therefore defined by their selectivity for uptake into the intestinal lymphatics as opposed to the blood capillaries in the subepithelial space. Because selectivity for the lymphatics is primarily defined by size, it is apparent that only macromolecules or colloids will be preferentially absorbed into the intestinal lymphatics. However, the intestine provides a significant barrier to the absorption of both macromolecules and intact colloids, and the most prevalent mechanism for drug delivery to the intestinal lymph is by means of secondary drug association with intestinal lipoproteins [110]. The size of the drug-lipoprotein complex subsequently dictates absorption into the lymphatic vessels. 

In summary it can be said that there are a lot of possibilities available to overcome the efflux pump-mediated absorption barrier in the intestinal tract. Further, more selective or more potent inhibitors will follow but it has to be carefully decided for each drug or therapy which type or class of inhibitor or efflux pump modulator might be best suited. Also drug delivery systems combining different efflux pump modulating properties have to be investigated in the future. 

The term mucoadhesion is commonly used to describe an interaction between the mucin layer, which lines the entire GI tract, and a bioadhesive polymer, which could be natural or synthetic in origin.From the oral delivery standpoint, these systems are used to immobilize and localize a drug delivery device in the selected regions of the GI tract, which could be an oral cavity (buccal and sublingual routes), the esophagus, stomach, small intestine, or colon (oral route). For the most part, research in this area has focused on the design of polymeric micro- and nanoparticulate systems that use hydrophilic polymers, primarily due to their propensity to interact with the mucosal surface. ... 

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... 

More recently, increasing research attention has focused upon the use of mucoadhe-sive delivery systems in which the biopharmaceutical is formulated with/encapsulated in molecules that interact with the intestinal mucosa membranes. The strategy is obviously to retain the drug at the absorbing surface for a prolonged period. Non-specific (charge-based) interactions can be achieved by the use of polyacrylic acid, whereas more biospecihc interactions are achieved by using selected lectins or bacterial adhesion proteins. Despite intensive efforts, however, the successful delivery of biopharmaceuticals via the oral route remains some way off. 

It is well known that intestinal M cells have the ability to efficiently transcytose macromolecules and inert particles, which has stimulated researchers to target M cells for oral delivery of macromolecular drugs and particles.26,52 For example, Ulex europaeus 1 (UEAl), a lectin specific for a-L-fucose residues, selectively binds to mouse Peyer s patch M cells.56 It has become apparent that UEAl can be used to target macromolecules to mouse Peyer s patch M cells and to enhance macromolecular... 

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