Despite numerous advances in the pathological mechanism of
inflammatory bowel disease (IBDs), the ideal
therapy is still missing.
N-Acylethanolamine-hydrolyzing
acid amidase (NAAA), a
cysteine hydrolase that deactivates
fatty acid ethanolamides, has been recognized as a new therapeutic target for IBDs. Herein, we proposed liposomal F96, a selective and potent NAAA inhibitor, as a new
therapy for IBDs. F96, with an IC50 of 270 nM for NAAA, was encapsulated into anionic
liposome and the anti-inflammatory activity was evaluated in
dextran sulfate sodium (DSS) induced
colitis mice. The anionic
liposomes showed significantly higher accumulation in the colon compared with the small intestine and cecum at 6 and 10 h after administration in DSS induced
colitis mice. DSS induction significantly increased
myeloperoxidase (MPO) activities and shortened the colon length, while free F96 significantly lowered tissue MPO activity and restored the colon length. Anionic
liposome encapsulation significantly enhanced the therapeutic efficacy of F96, as liposomal F96 resulted in lower MPO activity and better colon length restoration effects compared with those treated with free F96. This study offers a new treatment option for
colitis, which may pave the way for new
therapies for other IBDs.