Budesonide-liposomes inclusion complex in thermosensitive gel alleviates DSS-induced ulcerative colitis in mice

PurposeA novel formulation for Ulcerative Colitis (UC) treatment by rectal administration with budesonide liposomes (Bud (Lip)) and thermosensitive gel (Gel) was developed for future clinical use. To evaluate the anti-inflammatory activity and colon mucosal protection of this novel formulation compared with the other three in mice.MethodsBud (Lip) was prepared by reverse evaporation method and then dispersed in solutions with PL407 and PL188 by a cold method. Male mice were induced to UC by dextran sulfate sodium (DSS) and were treated for 14 days by rectal administration, as follows: Bud (enema) (a conventional suspension formulation); Bud (Lip); Bud (Gel); Bud (Lip-Gel); saline. And a negative control without colitis was also used. Disease activity index (DAI), and macroscopic and microscopic damage scores in colon tissues were used to evaluate the effect of therapy. The levels of IL-6 and IL-10 in serum and the concentrations of TNF-alpha and IL-10 and myeloperoxidase (MPO) activity in colon tissue were also introduced.ResultsIn UC mice model, Bud (Lip-Gel) showed inflammation was alleviated significantly, and the treatment was highly associated with lower DAI, less macroscopic and microscopic colonic damage and downregulation of pro-inflammatory cytokines TNF-alpha, IL-6 and MPO. Bud (Lip-Gel) had advantages over Bud, Bud (Lip), Bud (Gel) in the treatment of active UC.ConclusionNovel Bud liposomes complex in thermosensitive Gel effectively mitigated symptoms, alleviated macroscopic and microscopic colon damage, and reduced inflammatory reaction in UC mice, which might be a potential strategy for UC treatment.