Dual action tofacitinib-loaded PLGA nanoparticles alleviate colitis in an IBD mouse model

Area of Science:

• Biomaterials Science
• Gastroenterology
• Nanotechnology

Background:

• Inflammatory bowel disease (IBD) affects millions globally, with current treatments like tofacitinib citrate (TFC) causing significant systemic side effects.
• Targeted, localized drug delivery to inflamed gut tissues using nanoparticles (NPs) presents a strategy to mitigate these adverse effects.

Purpose of the Study:

• To optimize the synthesis of Poly(lactic-co-glycolic acid) (PLGA) 50:50 nanoparticles loaded with TFC for enhanced IBD treatment.
• To evaluate the in vitro drug release profile and in vivo efficacy of these TFC-loaded PLGA NPs in a colitis mouse model.

Main Methods:

• Nanoparticles (NPs) were synthesized using the nanoprecipitation method with a low molecular weight PLGA 50:50 grade loaded with TFC.
• In vitro drug release kinetics were characterized, and the efficacy of PLGA-TFC NPs was assessed in a C57BL/6 DSS colitis mouse model.

Main Results:

• TFC release from PLGA NPs exhibited a 40% burst release in the first hour, reaching up to 80% in a colonic environment.
• PLGA degradation by gut microbiota did not significantly alter TFC release kinetics.
• TFC-loaded PLGA NPs demonstrated significantly enhanced efficacy in mitigating weight loss in the colitis mouse model compared to PLGA NPs or TFC alone.

Conclusions:

• PLGA-TFC NPs show enhanced efficacy for IBD treatment, suggesting a potential for reduced dosage and fewer side effects.
• This nanoparticle delivery system represents a promising targeted therapy for IBD, improving TFC's therapeutic potential.