Polyester Nanoparticles and Polyurethane Nanocapsules Deliver Pirfenidone To Reduce Fibrosis and Scarring.

Pirfenidone has been shown to reduce fibrosis and modulate inflammation associated with conditions from pulmonary fibrosis to rheumatoid arthritis. It may also be useful for ocular diseases as well. However, for pirfenidone to be effective, it needs to be delivered to the tissue of interest, which, in the case of the eye, in particular, motivates the need for a system that permits local, long-term delivery to address the continuing pathology of the, condition. We investigated a set of delivery systems to determine the impact of encapsulation materials on the loading and delivery of pirfenidone. While the polyester system based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles exhibited higher loading than a polyurethane-based nanocapsule system, the delivery was short, with 85% of the drug being released in 24 h and no measurable drug after 7 days. Addition of different poloxamers impacted the loading but not the release of the drug. In contrast, the polyurethane nanocapsule system delivered 60% of the drug over the first 24 h and the remainder over the next 50 days. Furthermore, the polyurethane system permitted on-demand delivery via ultrasound. Being able to tune the amount of drug delivered via ultrasound has the potential to tailor the delivery of pirfenidone to modulate inflammation and fibrosis. We used a fibroblast scratch assay to confirm the bioactivity of the released drug. This work provides multiple platforms for the delivery of pirfenidone locally and over time in both passive and on-demand formulations with the potential to address a range of inflammatory and fibrotic conditions.