Targeting in the gastrointestinal tract: new approaches.

Most drug products are administered via the alimentary canal; prominent are the dosage forms which are swallowed, i.e., p.o. dosage forms, followed by those administered within the oral and the rectal cavities. The innermost surface of the alimentary canal is the epithelial lining which is void of keratinized superficial layers. The epithelium at both ends of the canal, i.e., oral cavity and esophagus, and anal canal is a multilayered (20-50 layers) stratified squamous epithelium, whereas that of the rest of the canal, i.e., gaster, small and large intestine and rectum is a single layer of columnar cells. The drainage is via both venous blood capillaries and lymphatic vessels. Blood drainage from the oral cavity and the lower end of the rectum is directly into systemic circulation via the vena cava. From the GI tract, however, the blood quantitatively passes through the portal vein and liver, hence is available for first-pass effect prior to entering systemic circulation. Targeting can be approached from two angles: 1) to exert the pharmacologic response at a specific site, or 2) to utilize a specific site for drug absorption. Targeting utilizes the anatomic, histologic, physiologic and biochemical features of various segments within the alimentary canal, paired with the design of special drug delivery systems or devices, and the use of special vehicle substances, such as polymers, bioadhesives, sorption promoters, or chemical modification (pro-drug) of the active moiety. Numerous examples of new types of drug delivery systems are presented. Many novel drug delivery systems discussed are still in experimental stage and evaluation, or even in the conceptual stage. However, it is anticipated that they all will contribute to further advancement in optimizing drug therapy.