To
mitigate the systemic adverse effects of tofacitinib, 5-ASA–PABA–MAC
and 5-ASA–PABA–diamine colon-specific delivery systems
were constructed, and tofacitinib azo prodrugs 9 and 20a–20g were synthesized accordingly. The release studies
suggested that these systems could effectively release tofacitinib in vitro, and the 5-ASA–PABA–diamine system
could successfully realize the colon targeting of tofacitinib in vivo. Specifically, compound 20g displayed
a 3.67-fold decrease of plasma AUC(tofacitinib, 0–∞) and a 9.61-fold increase of colonic AUC(tofacitinib, 0–12h), compared with tofacitinib at a molar equivalent oral dose. Moreover,
mouse models suggested that compound 20g (1.5 mg/kg)
could achieve roughly the same efficacy against ulcerative colitis
compared with tofacitinib (10 mg/kg) and did not impair natural killer
cells. These results demonstrated the feasibility of compound 20g as an effective alternative to mitigate the systemic adverse
effects of tofacitinib, and 5-ASA–PABA–MAC and 5-ASA–PABA–diamine
systems were proven to be effective for colon-specific drug delivery.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.