This study introduces a novel colon-targeted delivery system, NC-CS/PT-NPs, designed to address the limited solubility of Nitidine Chloride (NC) and enhance its therapeutic efficacy against nonalcoholic fatty liver disease (NAFLD). The nanoparticles were characterized, and their impact on NAFLD induced by a high-fat diet (HFD) in mice was investigated. Additionally, the study explores the influence of NC-CS/PT-NPs on the gut microbiota through 16S rDNA gene sequencing
Key Scientific Findings:
Nanoparticle Characterization:
- NC-CS/PT-NPs were successfully synthesized using the ion gel method.
- The nanoparticles exhibited an average particle size of 255.9±5.10 nm, encapsulation rate of 72.83±2.13%, and drug loading of 4.65±0.44%.
- In vitro release experiments demonstrated controlled release, with 66.75% cumulative release in the colon.
In Vivo Efficacy Against NAFLD:
- NC-CS/PT-NPs treatment inhibited weight gain, decreased serum AST, ALT, and lipid levels, and improved liver and intestinal inflammation in HFD-induced NAFLD mice.
- Histopathological analysis revealed enhanced disappearance of crypts and reduced inflammatory cell infiltration in treated mice.
Gut Microbiota Modulation:
- NC-CS/PT-NPs significantly altered the diversity of gut microbiota in HFD-induced NAFLD mice.
- The treatment increased the Firmicutes-to-Bacteroidetes ratio, reduced the abundance of Desulfobacterota, Campylobacterota, and Deferribacteres, and restored the abundance of beneficial bacterial families.
- Notable reductions in Oscillospirales and Campylobacterales were observed at the Order level.
Anti-Inflammatory Effects:
- NC-CS/PT-NPs decreased the levels of inflammatory cytokines TNF-α, IL-1β, and IL-6, indicating a potential to reduce liver inflammation in NAFLD.
Dual Stimulus-Responsive Nano-Carrier System:
- NC-CS/PT-NPs are designed to respond to both pH and intestinal microbiota stimuli.
- The dual stimulus-responsive system enhances the targeting of NC to the colon, improving therapeutic efficacy.
Clinical Implications:
- The study suggests that NC-CS/PT-NPs could be a promising drug delivery system for clinical applications of NC in NAFLD treatment.
- The formulation demonstrates superior efficacy compared to NC alone, emphasizing the importance of enhanced interaction with the gut microbiota.
Conclusion:
The synthesized NC-CS/PT-NPs present an innovative approach to address the solubility challenges of NC and enhance its therapeutic impact on NAFLD. The study provides comprehensive insights into the nanoparticle characterization, in vivo efficacy against NAFLD, modulation of gut microbiota, and anti-inflammatory effects. The dual stimulus-responsive nature of the nano-carrier system highlights its potential for clinical translation, opening avenues for further investigation and development in the field of drug delivery and NAFLD treatment.
Link to the the article : https://tinyurl.com/935h2swh
