Related Experiment Video
Updated: Jun 25, 2025
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
MnO2 and roflumilast-loaded probiotic membrane vesicles mitigate experimental colitis by synergistically augmenting
Chengjun Song1, Jiamin Wu1, Jinhui Wu1,2,3
1State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, 210093, China.
Background:
Ulcerative colitis (UC) is one chronic and relapsing inflammatory bowel disease. Macrophage has been reputed as one trigger for UC. Recently, phosphodiesterase 4 (PDE4) inhibitors, for instance roflumilast, have been regarded as one latent approach to modulating macrophage in UC treatment. Roflumilast can decelerate cyclic adenosine monophosphate (cAMP) degradation, which impedes TNF-α synthesis in macrophage. However, roflumilast is devoid of macrophage-target and consequently causes some unavoidable adverse reactions, which restrict the utilization in UC.
Results:
Membrane vesicles (MVs) from probiotic Escherichia coli Nissle 1917 (EcN 1917) served as a drug delivery platform for targeting macrophage. As model drugs, roflumilast and MnO2 were encapsulated in MVs (Rof&MnO2@MVs). Roflumilast inhibited cAMP degradation via PDE4 deactivation and MnO2 boosted cAMP generation by activating adenylate cyclase (AC). Compared with roflumilast, co-delivery of roflumilast and MnO2 apparently produced more cAMP and less TNF-α in macrophage. Besides, Rof&MnO2@MVs could ameliorate colitis in mouse model and regulate gut microbe such as mitigating pathogenic Escherichia-Shigella and elevating probiotic Akkermansia.
Conclusions:
A probiotic-based nanoparticle was prepared for precise codelivery of roflumilast and MnO2 into macrophage. This biomimetic nanoparticle could synergistically modulate cAMP in macrophage and ameliorate experimental colitis.
Insights
Engineered probiotic nanoparticles deliver roflumilast and MnO2 to macrophages, increasing cyclic adenosine monophosphate (cAMP) and reducing inflammation for ulcerative colitis (UC) treatment.
Area of Science:
- Biomedical Engineering
- Drug Delivery Systems
- Immunomodulation
Background:
- Ulcerative colitis (UC) is a chronic inflammatory bowel disease.
- Macrophages are implicated in UC pathogenesis.
- Current treatments like phosphodiesterase 4 (PDE4) inhibitors (e.g., roflumilast) have limitations due to off-target effects.
Purpose of the Study:
- To develop a targeted drug delivery system for UC treatment.
- To enhance the efficacy of roflumilast by co-delivery with MnO2.
- To investigate the modulation of macrophage activity and therapeutic effects in a colitis model.
Main Methods:
- Fabrication of membrane vesicles (MVs) from probiotic Escherichia coli Nissle 1917 (EcN 1917).
- Encapsulation of roflumilast and manganese dioxide (MnO2) into MVs (Rof&MnO2@MVs).
- In vitro assessment of cAMP and TNF-α levels in macrophages and in vivo evaluation in a mouse colitis model.
Main Results:
- Rof&MnO2@MVs effectively delivered drugs to macrophages.
- Co-delivery significantly increased cyclic adenosine monophosphate (cAMP) and decreased TNF-α production.
- Treatment with Rof&MnO2@MVs ameliorated experimental colitis and modulated gut microbiota composition.
Conclusions:
- Probiotic-derived MVs serve as an effective platform for targeted co-delivery of roflumilast and MnO2.
- This approach synergistically modulates macrophage cAMP levels, offering a promising therapeutic strategy for UC.
- The developed nanoparticle demonstrates potential for treating experimental colitis with improved safety and efficacy.
