Oral Administration of Cryptotanshinone-Encapsulated Nanoparticles for the Amelioration of Ulcerative Colitis

Background Inappropriate macrophages phenotype transition contributes to the development of ulcerative colitis, and the poly (ethylene glycol)-block-poly (d, l-lactic acid) (PEG-PLA) nanoparticles delivery system can be utilized to improve the cryptotanshinone (CTS)-based therapy. Methods We used a single emulsification method to prepare CTS-encapsulated nanoparticles (NPCTS). The therapeutic efficacy of NPCTS was evaluated in dextran sulfate sodium (DSS)-induced colitis mice. Then the proportion of total macrophages and M2-like macrophages were assayed with flow cytometry, and the relative content of pro-inflammatory cytokines in the colon was detected with Western blot. Bone-marrow-derived macrophages (BMDMs) were induced into M1-like macrophages, which were further incubated with NPCTS to repolarize into M2 subtype(.) Results Cryptotanshinone could induce the transition of M1 subtype to M2 subtype as indicated by up-regulated expression of arginase 1 (ARG1), interleukin (IL)-10, and CD206. In vivo, orally administrated NPCTS accumulated in the colon-infiltrated macrophages in colitis mice. It further revealed that NPCTS significantly alleviated colitis symptoms as indicated by increased body weight and colon length, decreased tumor necrosis factor (TNF)-alpha, IL-1 beta, and IL-6 content in the colon, and diminished total macrophage proportion (CD45(+)CD11b(+)F4/80(+)) and up-regulated M2 proportion (CD45(+)CD11b(+)F4/80(+)CD206(hi)). Conclusion Oral administration of NPCTS could ameliorate ulcerative colitis with the conversion of M1-like macrophages to M2-like macrophages.

Automated summary

It was found that oral administration of NPCTS could accumulate in the colon of colitis mice, significantly improve inflammation symptoms, reduce levels of inflammatory cytokines in the colon, decrease the proportion of total macrophages, and increase the proportion of M2-like macrophages.