| Description |
Novel pH sensitive hydrogels containing azoaromatic crosslinks were synthesized by the crosslinking of polymeric precursors. First, a reactive polymeric precursor was synthesized by copolymerization of N,N-dimethylacrylamide, N-tert.-butylacrylamide, acrylic acid, and N-methacryloylglycylglycine p-nitrophenyl ester. The hydrogel was prepared in the second step by the reaction of the polymeric precursor with N,N'-(omega-aminocaproyl)-4,4'-diaminoazobenzene. These hydrogels are suitable for colon-specific peptide or protein delivery. In the low pH 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 swelling 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 characterized by the network structure (i.e., content of crosslinks, unreacted pendent groups, and cycles), the equilibrium and dynamic swelling as a function of pH, modulus of elasticity, and in vitro/ in vivo degradation. The results indicated that the hydrogel network structure strongly depends on the reaction conditions such as polymer concentration, and the ratio of the reactive groups during the crosslinking reaction. The swelling and mechanical properties of hydrogels can be controlled by the modification of polymer backbone structure and/or the crosslinking density. Depending on the network structure, the degradation of hydrogels followed either a surface erosion or a bulk-degradation-like process. In vivo degradation rate of hydrogels was three to five times faster than that of in vitro, indicating a higher azoreductase activity in vivo. A gel-coated capsule device was formulated for the oral delivery of insulin. Its mechanical properties and the rate of insulin release were found to be related to the degree of swelling of the coated gel layers. The higher the swelling, the higher the amount of insulin released, and the weaker the mechanical strength of the coated capsule. Effect of a penetration enhancer, namely of CapMul MCM (a medium chain glyceride) on physiological properties of rabbit intestinal 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 moderate change in ion transport in the colon, the increase in marker molecule permeabilities ranged between 7-25 times depending upon their molecular weight. |
