INTESTINAL DELIVERY

Keywords Drug transporter SLC-transporter ABC transporter Drug delivery Intestinal absorption barrierl... 

Delivery systems that respond to changes in pH have been known to the pharmaceutical industry for more than a century. The pH-sensitive enteric coating is probably the oldest controUed-release technology. Unna introduced an enteric tablet coating based on keratin in 1884 (108). Enteric coatings are used primarily to protect the gastric mucosa from local irritation or to ensure that tablets do not dissolve until they reach the intestine. 

Delivery of peptides and proteins via the gastrointestinal tract has not been successful because of poor penetration through the intestinal epithelium and high levels of proteolytic activity in the gastrointestinal tract. Liposomal encapsulation of proteins and peptides will not improve the efficiency and capacity of this absorption pathway considerably (e.g., Ryman et al., 1982 Machy and Leserman, 1987 Weiner and Chia-Ming Chiang, 1988). These difficulties in delivery via the oral route caused the parenteral route to remain the preferred route for the administration of therapeutic peptides... 

Because of its convenience and good patient compliance, oral administration is the most preferred drug delivery form. As a result, much of the attention of in silico approaches is focused on modeling drug oral absorption, which mainly occurs in the human intestine. In general, drug bioavailability and... 

Yu LX, Lipka E, Crison JR and Amidon GL. Transport approaches to the bio-pharmaceutical design of oral drug delivery systems prediction of intestinal absorption. Adv Drug Deliv Rev 1996 19 359-76. 

Most pancreatic enzyme supplements are enteric coated to release enzymes in the alkaline environment of the intestine this minimizes enzyme destruction in the stomach. Enteric-coated pancreatic enzyme supplements require fewer daily dosage units, but delivery of the drug to the site of action and effectiveness may be delayed by gastric emptying time.41... 

Parenteral nutrition can be a lifesaving therapy in patients with intestinal failure, but the oral or enteral route is preferred when providing nutrition support ( when the gut works, use it ). Compared with PN, enteral nutrition generally is associated with fewer infectious complications (e.g., pneumonia, intraabdominal abscess, and catheter-related infections) and potentially improved outcomes.1-3 However, if used in appropriate patients (i.e., patients with questionable intestinal function or when the intestine cannot be used), PN can be used safely and effectively and may improve nutrient delivery.4 Indications for PN are listed in Table 97-1.1... 

The promise of the isolation and production of therapeutic polypeptides and proteins demands that for treatment of a chronic disease state an oral delivery system be developed which will protect these valuable agents from the hostile gastric environment. Subsequently, the drugs will have to be completely released in the intestine, preferably in a state that will enhance their rapid dissolution and transport across the gut wall minimizing interaction with intestinal proteases. 

There are circumstances, however, where blood flow to the GIT may influence drug absorption. Those compounds absorbed by active or specialized mechanisms require membrane participation in transport, which in turn depends on the expenditure of metabolic energy by intestinal cells. If blood flow and therefore oxygen delivery is reduced, there may be a reduction in... 

As with micelle-facilitated dissolution, emulsion-facilitated dissolution has gained renewed interest due to its application to water-insoluble drug delivery and enhanced absorption. Over the years, emulsion systems have been developed and used to either model the in vivo dissolution process or mimic the intestinal surfactant system to enhance drug delivery of poorly soluble compounds [54-66], Emulsions have also been used as vehicles for drug delivery, e.g., to protect... 

LZ Benet, CY Wu, MF Hebert, VJ Wacher. Intestinal drug metabolism and antitransport processes A potential paradigm shift in oral drug delivery. J Controlled Release 39 139-143, 1996. 

Some extended-release preparations are designed with a coating that responds to the acidity of its environment. The polymeric coating of the medicine is formulated for stability during oral delivery and for eventual solubility at the intended organ. The contrasting acidic content of the stomach and the more basic environment of the intestines enable these formulations to function. For example, hydroxypropyl methylcellulose phthalate (HPMCP) (Fig. 14.1.3) is an enteric... 

Attempts to study the entry of ES products into cells using markers of fluid phase endocytosis yielded unexpected results. When larvae browse resistant IEC-6 cells in the presence of extracellular fluorescent dextran, dextran enters the cytoplasm of a significant proportion of the cells in the mono-layer (Butcher et al., 2000). The parameters of dextran entry are most compatible with the conclusion that larvae wound the plasma membranes of IEC-6 cells that is, they create transient breaches in the membrane that allow impermeant markers to enter the cell (McNeil and Ito, 1989). Wounding is considered to be a common occurrence in intestinal epithelia (McNeil and Ito, 1989). Injured cells are able to heal their wounds by recruiting vesicles to seal the breach (Steinhardt et al., 1994). In an experimental system, healing allows the injured cell to retain cytoplasmic dextran. In epithelial cell cultures inoculated with T. spiralis larvae, the relationship between glycoprotein delivery and injury of plasma membranes is not clear, i.e. dextran-laden cells do not always stain with Tyv-specific antibodies and... 

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