Azo chemistry and its potential for colonic delivery

Abstract

Improved delivery systems are needed for drugs currently in use to treat localized diseases of the colon. One promising approach is to deliver the drugs specifically to the colon, an approach that has gained importance recently in the treatment of these diseases. The advantages of targeting drugs specifically to the diseased colon include fewer systemic side effects, a need for lower doses of drugs, and maintenance of the drug in its intact form close to the target site. The potential for colon-specific delivery of therapeutic proteins and peptides is also of interest. To achieve colon-specific drug delivery following oral administration, the drug needs to be protected from absorption by the upper gastrointestinal tract and from degradation by the upper gastrointestinal tract environment, allowing the drug to be abruptly released into the proximal colon. One strategy for targeting orally administered drugs to the colon exploits carriers that are degraded specifically by colonic bacteria and utilizes microbially degradable polymers/drugs, especially azo-cross-linked polymers/drugs. Prodrugs utilizing azo linkages are sulfasalazine, ipsalazine, balsalazine, and olsalazine. These were developed for delivery of 5-amino salicylic acid to the colon for localized chemotherapy of inflammatory bowl disease. The azo-conjugation approach utilizes the ability of the colonic environment to cleave these conjugates and protects the drug from absorption or degradation in the upper gastrointestinal tract. It is believed that flavin mediators present in the colon and azo-reductase enzymes released from colonic bacteria are responsible for the degradation of azo-aromatic compounds for site-specific delivery of the drug to the colon.