SITE-SPECIFIC DRUG-DELIVERY AND PENETRATION ENHANCEMENT IN THE GASTROINTESTINAL-TRACT

New types of biodegradable and pH-sensitive hydrogels were synthesized by the crosslinking of polymeric precursors. They contained both acid ic comonomer and enzymatically degradable azoaromatic crosslinks. Such hydrogels are suitable for colon-specific drug delivery. In the low p H range of the stomach, the swelling of the gel is low and the drug is protected against digestion by enzymes. In the small intestine, the s welling increases. Upon arrival in the colon, a degree of swelling is reached that makes the crosslinks accessible to azoreductase activity. The gel is degraded and drug released. The hydrogels were characteriz ed by the network structure (i.e., content of crosslinks, unreacted pe ndent groups, and cycles), the equilibrium and dynamic swelling as a f unction of pH, modulus of elasticity, and in vitro/in vivo degradation , The results indicated that the hydrogel network structure strongly d epends on the reaction conditions such as polymer concentration, and t he ratio of the reactive groups during the crosslinking reaction. The swelling and mechanical properties of hydrogels can be controlled by t he modification of polymer backbone structure and/or the crosslinking density. Depending on the network structure, the degradation of hydrog els followed either a surface erosion or a bulk-degradation-like proce ss. In vivo degradation rate of hydrogels was three to five times fast er than that in vitro. The effect of a penetration enhancer, CapMul MC M (a medium chain glyceride), on physiological properties of rabbit in testinal epithelium was investigated in vitro using the Ussing chamber technique. It was shown that CapMul MCM affected tissue ion transport , permeability, and morphology in a concentration- and time-dependent manner. It was found that with minimal epithelial disruption and moder ate change in ion transport in the colon, the increase in marker molec ule permeabilities ranged between 7 and 25 times depending upon their molecular weight.