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

Area of Science:

• Biomaterials Science
• Ophthalmology
• Drug Delivery

Background:

• Pirfenidone is a potent anti-fibrotic and anti-inflammatory agent with therapeutic potential in various conditions, including ocular diseases.
• Effective treatment of ocular diseases requires localized, long-term delivery of pirfenidone to the target tissue.
• Current delivery systems often lack the necessary duration or control for sustained therapeutic effects.

Purpose of the Study:

• To investigate and compare the efficacy of different encapsulation materials for pirfenidone delivery.
• To evaluate the loading capacity and release kinetics of pirfenidone from various nanocarrier systems.
• To assess the potential for on-demand drug release and confirm the bioactivity of delivered pirfenidone.

Main Methods:

• Fabrication and characterization of poly(lactic-co-glycolic acid) (PLGA) nanoparticles and polyurethane (PU) nanocapsules for pirfenidone encapsulation.
• In vitro assessment of drug loading efficiency and release profiles over time for both systems.
• Investigation of poloxamer effects on drug loading and release kinetics.
• Evaluation of ultrasound-triggered, on-demand drug release from PU nanocapsules.
• Confirmation of pirfenidone bioactivity using a fibroblast scratch assay.

Main Results:

• PLGA nanoparticles demonstrated higher initial pirfenidone loading but rapid release (85% in 24 hours, undetectable by 7 days).
• Polyurethane nanocapsules exhibited sustained pirfenidone release, with 60% released in 24 hours and the remainder over 50 days.
• Addition of poloxamers influenced drug loading but not the release rate.
• The PU nanocapsule system successfully demonstrated on-demand pirfenidone delivery triggered by ultrasound.
• Released pirfenidone from PU nanocapsules retained bioactivity in fibroblast scratch assays.

Conclusions:

• Polyurethane nanocapsules represent a promising platform for sustained, localized, and on-demand delivery of pirfenidone for ocular inflammatory and fibrotic conditions.
• The ability to tune pirfenidone release via ultrasound offers a novel approach for personalized therapeutic strategies.
• This research provides versatile delivery platforms for pirfenidone, potentially applicable to a range of fibrotic and inflammatory diseases.