Microfluidic techniques in the development of PLGA nanoparticles: a tri-combination therapy for paraquat-induced cytotoxicity

Introduction

Paraquat (PQ) is a widely used herbicide that is highly toxic to humans, particularly causing acute lung injury and pulmonary fibrosis. Current treatments are limited and largely ineffective, with no specific antidote available. To address this, researchers explored the use of poly(lactic‑co‑glycolic acid) (PLGA) nanoparticles as carriers for three therapeutic agents—Pirfenidone (PFD), Quercetin (Que), and 4‑Octyl Itaconate (4‑OI)—to enhance drug delivery and improve protective effects against PQ‑induced cytotoxicity.

Why This Research Matters

PQ poisoning remains a major global health challenge with high mortality rates and limited therapeutic options. Combining multiple drugs in a nanocarrier system offers a promising strategy to overcome poor bioavailability, reduce side effects, and achieve synergistic therapeutic effects. This approach could provide a novel treatment pathway for paraquat poisoning and its severe pulmonary complications.

Key findings

The study successfully synthesized PLGA nanoparticles loaded with Que, 4‑OI, and PFD using a microfluidic method. The nanoparticles showed favorable characteristics, including small size (~166–173 nm), narrow polydispersity, high entrapment efficiency (~65%), and stability over 30 days. In vitro assays demonstrated that PLGA‑based combination therapy significantly improved cell viability in lung fibroblasts compared to free drugs, while reducing oxidative stress markers (ROS, lipid peroxidation, protein carbonyls) and increasing glutathione levels. The PLGA triple combination therapy was more effective at lower doses than the free‑drug combination.

Conclusion

Delivering Que, 4‑OI, and PFD through PLGA nanoparticles provides a synergistic and potent protective effect against PQ‑induced cytotoxicity. This nanocarrier‑based therapy reduces oxidative damage, enhances antioxidant defenses, and improves cell survival, making it a promising candidate for future treatment of paraquat poisoning and related lung injuries.

 Full Article Reference

Title: Microfluidic techniques in the development of PLGA nanoparticles: a tri-combination therapy for paraquat-induced cytotoxicity
Journal: Toxicology Research, 2025
DOI: https://doi.org/10.1093/toxres/tfaf133