Gastrointestinal tract targeting

Gad, S. C. 2007. Toxicology of the gastrointestinal tract. Target organ toxicology series, vol. 24. Boca Raton, FL CRC Press. 

Polymeric microparticles have been studied and developed for several years. Their contribution in the pharmacy field is of utmost importance in order to improve the efficiency of oral delivery of drugs. As drug carriers, polymer-based microparticles may avoid the early degradation of active molecules in undesirable sites of the gastrointestinal tract, mask unpleasant taste of drugs, reduce doses and side effects and improve bioavailability. Also, they allow the production of site-specific drug targeting, which consists of a suitable approach for the delivery of active molecules into desired tissues or cells in order to increase their efficiency. 

The important stages in delivering a drug to its desired target after an oral dose can be summarized as shown in Fig. 6.2. Initially the formulation has to be swallowed and survive the transition to the site of absorption - the gastrointestinal tract (GIT). The time required for this to happen will depend on the stomach emptying time, which in turn will be a function of the fed/fasted state of the subject or animal that is being studied (see for example Ref. [7]). This kind of information can only be obtained from in vivo studies. 

The gastrointestinal tract is conveniently divided into a number of areas, primarily on the basis of morphology and function. For most pharmaceutical purposes, we can group the target tissues into three regions the upper, mid- and lower gastrointestinal tract. 

We will discuss in more detail in Chapter 8 how intracellular copper levels are maintained at extremely low levels by a series of copper chaperone proteins, which sequester newly assimilated copper within the cytoplasm of cells and deliver it in a targeted manner to be incorporated into specific copper-containing proteins. While copper uptake across the gastrointestinal tract is poorly understood—most probably utilising the divalent cation transporter... 

Intravenous Administration When a drug is injected, the entire dose can be considered as being available in the bloodstream to be distributed to the target site. Hence, the dosage can be controlled, unlike with other routes of administration, where the bioavailability of the drug may be unpredictable because of diffusion processes. Intravenous injection is the normal route for administration of protein-based drugs, as they are likely to be destroyed if taken orally because of the pH conditions in the gastrointestinal tract. 

The three targets that are the first point of contact between environmental chemicals and the body will be discussed first the gastrointestinal tract, the respiratory system, and the skin. Recall from Chapter 2 that chemicals enter the blood after absorption, so this fluid is the next target (see Figure 2.1). Then come the liver, the kidneys, and the nervous system. The chapter concludes with a discussion of some chemicals that can damage the reproductive system and some that can cause birth defects, the so-called teratogens, and other forms of developmental toxicity. Brief discussions of immune system, cardiovascular system, muscle, and endocrine system toxicities are also offered. 

Pacifici, G.M., Franchi, M., Bencini, C., Repetti, F., Di Lascio, N., and Muraro, G.B., Tissue distribution of drug-metabolizing enzymes in humans, Xenobiotica, 18 849-856 (1988). Ritschel, W.A., Targeting in the gastrointestinal tract new approaches. Methods Find. Exp. Clin. Pharmacol., 13 313-336 (1991). 

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