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

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https://pubs.acs.org/doi/10.1021/acsbiomaterials.3c00087

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https://doi.org/10.1021/acsbiomaterials.3c00087
 http://hdl.handle.net/11603/28259

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https://orcid.org/0000-0002-0644-744X

Date

2023-05-17

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journal articles
postprints
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Citation of Original Publication

Liu, Shuaishuai, et al. "Polyester Nanoparticles and Polyurethane Nanocapsules Deliver Pirfenidone To Reduce Fibrosis and Scarring" ACS Biomaterials Science & Engineering 9, no. 6 (17 May, 2023): 3348-3355. https://doi.org/10.1021/acsbiomaterials.3c00087.

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This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Biomaterials Science & Engineering, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsbiomaterials.3c00087.
Access to this item will begin on 05/17/2024

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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 material on 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 hours an no measurable drug after 7 days. Addition of different poloxamers impacted the loading but not release of the drug. In contrast, the polyurethane nanocapsule system delivered 60% of the drug over the first 24 hours 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 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.