Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
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alsfakia@gmail.com

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Σάββατο 1 Δεκεμβρίου 2018

Nanoparticle-mediated local delivery of pioglitazone attenuates bleomycin-induced skin fibrosis

Publication date: Available online 1 December 2018

Source: Journal of Dermatological Science

Author(s): Mai Kanemaru, Jun Asai, Jun-ichiro Jo, Takahiro Arita, Minako Kawai-Ohnishi, Miho Tsutsumi, Makoto Wada, Yasuhiko Tabata, Norito Katoh

Abstract
Background

Nanoparticle-loaded delivery systems have attracted much attention recently. Poly(lactic-co-glycolic acid) (PLGA) is one of the most successful biodegradable polymers for biomedical applications. There are only a few studies on the treatment of dermal fibrosis with sustained-release drugs. Peroxisome proliferator-activated receptor-γ (PPAR-γ) plays an important role in endogenous anti-fibrotic defense mechanisms. Recent studies have suggested that pioglitazone, a synthetic PPAR-γ activator, has effects beyond reducing blood sugar and it can reduce fibrosis and inflammation when used systemically.

Objective

We aimed to assess the effects of local injections of pioglitazone-loaded PLGA nanoparticles (PGN-NP) on an experimental sclerosis and to demonstrate the in vivo pharmacokinetics of subcutaneously administered PLGA nanoparticles.

Methods

Locally injectable PGN-NP were prepared and subcutaneously administered to bleomycin (BLM)-induced scleroderma model mice. The effect of pioglitazone was also evaluated with cultured fibroblasts. Coumarin-6-loaded fluorescent PLGA nanoparticles (FL-NP) and silicon naphthalocyanine-loaded near-infrared PLGA nanoparticles (NIR-NP) were used to demonstrate in vitro cellular uptake by cultured fibroblasts and the in vivo pharmacokinetics of subcutaneously administered nanoparticles.

Results

Weekly subcutaneous injections of PGN-NP attenuated skin fibrosis in BLM-induced scleroderma model mice. Pioglitazone significantly suppressed migration ability and TGF-β-mediated myofibroblast differentiation in cultured fibroblasts. FL-NP were internalized into cultured fibroblasts within 60 min, and PGN-NP-primed fibroblasts expressed anti-fibrotic phenotypes. Subcutaneously injected NIR-NP remained in the vicinity of the injection site more than non-particulate silicon naphthalocyanine.

Conclusion

These results provide a basis for the development of new treatments for dermal fibrosis and a better understanding of the potential of



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