| Popis: |
The rapid scientific progress in the areas of gene technology and biotechnology has provided an increasing number of biologically active compounds, raising the hope that better cures will be available in the near future for a number of severe diseases. However, before such novel biopharmaceuticals (e.g., peptides, proteins, oligonucleotides, gene vectors) can be used for drug therapy in humans, novel ways of drug delivery have to be developed in order to ensure the safe and effictent administration of these compounds to the patient (For general references, see refs 1-4). Certainly, convenient and easy routes of drug administration- ideally by simply swallowing a tablet or capsule-would be preferable to parenteral injections, which are painful and require trained healthcare personnel However, because of their relatively large size, poor lipid solubility, and delicate structure-in contrast to many conventional small drug molecules-the transport of modern biopharmaceuticals across biological barriers, such as epithelial tissues or the membranes of individual cells themselves, is usually very slow. Moreover, the residence time of drugs or drug delivery systems at a given mucosal absorption barrier may be relatively short This limits the time available for drug absorption before the compound is either metabolically destroyed or swept away by mechanical clearance processes (e.g., mucus secretion and transport, bowel movements, coughing, sneezing, and so on). Both problems, namely to control and prolong the residence time of the compound to be delivered at a given biological barrier, and to increase the rate at which the compound is transported across this barrier, might be solved by employing bioadhesive drug delivery systems (6-8. The first such systems were based on mucoadhesive polymers, which "stick" to wet mucous surfaces by nonspecific, physicochemical mechanisms (e.g., hydrogen bonding, swelling, polymer chain interpenetration, and surface energy effects). More recently, however, lectins have attracted the interest of pharmaceutical scientists, because of their ability to accomplish specific binding to membrane-bound receptors located at the luminal surface of epithelial cells (9). |
