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Paederia scandens-derived exosome-like nanoparticles as a delivery system for andrographolide to treat ulcerative
Yuxuan Peng1, Vadim Demidchik2, Yan Li3
1Department of Veterinary Internal Medicine, Faculty of Veterinary Medicine, Huazhong Agricultural University, 1 Shizishan St., Hongshan District, 430070 Wuhan, China; Department of Plant Cell Biology and Bioengineering, Faculty of Biology, Belarusian State University, 4 Independence Ave., 220030 Minsk, Belarus; Hainan College of Vocation and Technique, 95 Nanhai Ave., 570100 Haikou, China.
Abstract:
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing colon inflammation. Side effects and drug resistance limit current therapies. Andrographolide (AG), an NF-κB pathway inhibitor, shows promise in UC treatment but suffers from poor oral bioavailability. In this study, Paederia scandens-derived exosome-like nanoparticles (P-ELNs) were used as a delivery system to enhance the therapeutic efficacy of AG in UC. P-ELNs were extracted from Paederia scandens leaves and characterized for size, zeta potential, and morphology using transmission electron microscopy (TEM) and nanoparticle tracking analysis. AG was loaded into P-ELNs (AG-P-ELNs), and the complex was characterized for encapsulation efficiency using high-performance liquid chromatography (HPLC). The anti-inflammatory effects of AG, P-ELN, and the AG-P-ELNs complex were assessed in LPS-stimulated RAW264.7 macrophages (in vitro) and in a dextran sulphate sodium (DSS)-induced colitis mouse model (in vivo). According to the results, AG-P-ELNs demonstrated a high encapsulation efficiency of 38.64 % and a stable dispersion system with a zeta potential of -38.55 mV, indicating good colloidal stability. In vitro, AG-P-ELNs significantly reduced the production of pro-inflammatory cytokines IL-1β, IL-6, IL-18 and TNF-α, promoting M1 macrophage polarized to M2. In vivo, AG-P-ELN treatment ameliorated DSS-induced colitis, normalized colon length, and mitigated inflammatory cell infiltration. The AG-P-ELN group showed the lowest NF-κB, NLRP3, and iNOS expression, suggesting a synergistic therapeutic effect in modulating macrophage polarization and inflammation. P-ELNs effectively enhance the bioavailability and therapeutic efficacy of AG in treating UC by improving its solubility, stability, and cellular uptake while modulating macrophage polarization and inflammation. This study provides a novel approach for the delivery of AG and highlights the potential of plant-derived nanoparticles in inflammatory bowel disease management.
Insights
Paederia scandens exosome-like nanoparticles (P-ELNs) effectively deliver andrographolide (AG) to treat ulcerative colitis (UC). This novel approach enhances AG
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Pharmacology
Background:
- Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited therapeutic options due to side effects and drug resistance.
- Andrographolide (AG), a potent NF-κB inhibitor, shows therapeutic potential for UC but has poor oral bioavailability.
- Novel drug delivery systems are needed to enhance AG's efficacy for UC treatment.
Purpose of the Study:
- To develop and evaluate Paederia scandens-derived exosome-like nanoparticles (P-ELNs) as a delivery system for andrographolide (AG).
- To investigate the enhanced therapeutic efficacy of AG-loaded P-ELNs (AG-P-ELNs) in treating ulcerative colitis (UC) both in vitro and in vivo.
- To assess the impact of AG-P-ELNs on inflammatory pathways and macrophage polarization in UC models.
Main Methods:
- P-ELNs were extracted from Paederia scandens leaves and characterized using TEM and nanoparticle tracking analysis.
- AG was loaded into P-ELNs, and encapsulation efficiency was determined by HPLC.
- Anti-inflammatory effects were evaluated in LPS-stimulated RAW264.7 macrophages and a DSS-induced colitis mouse model.
Main Results:
- AG-P-ELNs exhibited high encapsulation efficiency (38.64%) and good colloidal stability (zeta potential: -38.55 mV).
- In vitro, AG-P-ELNs significantly reduced pro-inflammatory cytokines (IL-1β, IL-6, IL-18, TNF-α) and promoted M1 to M2 macrophage polarization.
- In vivo, AG-P-ELNs ameliorated DSS-induced colitis, improved colon length, reduced inflammatory infiltration, and suppressed NF-κB, NLRP3, and iNOS expression.
Conclusions:
- P-ELNs serve as an effective delivery system, enhancing AG's bioavailability, solubility, stability, and cellular uptake for UC treatment.
- AG-P-ELNs demonstrate synergistic therapeutic effects by modulating macrophage polarization and key inflammatory pathways.
- Plant-derived nanoparticles offer a promising strategy for managing inflammatory bowel diseases like UC.
