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

Abstract

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.

Polyurethane Nanoparticles as Versatile Tools in Nanomedicine: A Review

“…It has also been demonstrated that polymeric polyurethane micelles and nanoparticles are effective medication delivery and transportation nanovehicles. Liu et al successfully encapsulated pirfenidone in a polyurethane-based nanocapsule and compared it with the pirfenidone-loaded PLGA nanoparticles to reduce fibrosis for the treatment of ocular diseases. According to their studies, PLGA particles can activate compliments which leads to angiogenesis associated with AMD (age-related macular degeneration).…”

“…Therefore, using polyurethane nanoparticles for the delivery of pirfenidone is more suitable as it does not activate compliments. Furthermore, the polyurethane system permitted on-demand delivery via ultrasound for the treatment of fibrosis …”

Pirfenidone: A Promising Drug in Ocular Therapeutics

“…Long-term, patients with AMD may benefit more from this, as it may improve their prognoses. [12] 5-fluorouracil, or 5-FU, is a medication that prevents the formation of cells that create scar tissue, which may impede vision and lead to difficulties after eye surgery. A number of ocular and periorbital procedures, including pterygium surgery, dacryocystorhinostomy, vitreoretinal surgery, and glaucoma filtering surgery, employ it as an adjuvant therapy.…”

“…This includes the management of irregular astigmatism resulting from disrupted wound healing processes. [50,51] Given the observed effects of pirfenidone in promoting the healing of corneal abrasion wounds, as well as its impact on mitigating fibrosis and scarring, [4,5,12,44] it is reasonable to consider pirfenidone as a viable candidate for treating ulcerative keratitis. Such a treatment approach could provide an alternative to the existing methods currently utilized in ocular clinical settings.…”

“…Additionally, ongoing research is exploring the potential of pirfenidone in other ocular disorders such as corneal fibrosis and ocular surface diseases. [12,13] These studies have shown its potential in promoting the healing of corneal wounds, treating ocular trauma, reducing corneal fibrosis and inflammation, preserving visual clarity, managing age-related macular degeneration (AMD), addressing proliferative vitreoretinopathy, and playing a prominent role in postoperative glaucoma surgery (Figure 2). [14][15][16][17][18][19][20][21] In recent years, pirfenidone has gained immense popularity and has been the subject of numerous research publications and patented technologies in ophthalmology.…”