Gastrointestinal barrier

Fig. 8.6 Depiction of gastrointestinal barriers to oral peptide drug delivery and strategies to overcome them by the use of multifunctional matrices. Adapted from Bernkop-Schnurch and Walker (2001)...

Aluminum enters the human organism via the gastrointestinal (water, beverages, drugs, cosmetics, foods) or respiratory apparatus (inhaled dust), by intranasal absorption to the brain, and by transdermal absorption [15]. Most of the metal is excluded by intervention of the gastrointestinal barrier and by renal function. Also, some accumulation occurs in the entire body, including brain, heart muscle, bones, and lungs (Fig. 1). 

The gastrointestinal barrier is considered to comprise two components the intrinsic barrier, composed of epithehal cells lining the digestive tube and the tight junctions that tie them together and the extrinsic barrier, consisting of secretions and other influences that are not physically part of the epithehum but which affect the epithelial cells and maintain their barrier function (Table 4.1). 

Tight junctions between epithelial cells seal the paracellular spaces and establish the basic gastrointestinal barrier. 

Paneth cells contribute to the maintenance of the gastrointestinal barrier, by secreting a number of antimicrobial molecules (alpha-defensins or cryptidins), as well as lysozyme and phospholipase A2. Their location, adjacent to crypt stem cells, suggests they have a role in defending epithelial cell renewal. 

However, intensive studies are in progress today in the biopharmaceutical industry for the application of alternate delivery systems, and future advances in medical therapies will depend on new deliveries. These new deliveries may focus on modified parenteral system(s), as well as cavitational, respiratory, gastrointestinal, nasal, dermal, and other areas. In each case, membrane and gastrointestinal barriers must be extensively studied in order to increase bioavailability. 

In mammals, inorganic tin salts are practically insoluble and do not pass through the gastrointestinal barrier (Fritsch etal. 1977). Absorbed tin is probably bound to red blood cells, gradually concentrated by cells of the reticuloendothelial system, and then eventually excreted by the kidney. Some tin is deposited in lung and bone. 

Nanoparticles, due to their unique properties and surface characteristics, can protect the drug from P-gp, cytochrome P-450, and the destructive factors in the GI tract and can increase the permeability of drugs through the gastrointestinal barrier [62]. These reports confirm that nanoparticulate systems with unique properties can increase the transport of many compounds across the GI barrier. Numerous examples of nanoparticles being used to deliver antibodies, cytokines, other proteins, and drug substances into specific cells or tissues with good safety and trustworthiness are reported in the literature [49, 71,85]. 

Schenk M, Mueller C. The mucosal immune system at the gastrointestinal barrier. Best Pract Res Clin Gastroenterol. 2008 22391-409. 

In the 1980s, research into the plaques and fibres in the brains of people with Alzheimer s disease suggested that aluminium might be partly responsible for the condition. This now seems less likely. The World Health Organization sets a tolerable intake of aluminium for a 60 kg adult at 60 mg per day. For most people, the mass actually ingested daily is about 10 mg. Aluminium is mostly excreted in the faeces. That which passes across the gastrointestinal barrier into the blood stream is dealt with by the kidneys (Figure 9.18). 

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