Pirfenidone-loaded hyaluosomes as a nanocarrier for the treatment of scleroderma

Scleroderma is a chronic autoimmune disorder marked by excessive fibrosis and skin thickening. To improve treatment efficacy, this study developed and evaluated pirfenidone-loaded hyaluosomes (PFD-HSs) as an advanced nanocarrier system for the topical delivery of the antifibrotic agent pirfenidone. The optimized formulation; PFD-HS1 composed of lipoid S100, sodium cholate, and 0.5% hyaluronic acid achieved high entrapment efficiency 90.44%, a vesicle size of 125 nm, a PDI of 0.12, and a ZP of -26 with uniform spherical morphology and sustained in vitro drug release over 6 h. FTIR testing confirmed changes in the drug's physical state following formulation that suggest possible intermolecular interactions, potentially including hydrogen bonding. When incorporated into a topical gel, the formulation demonstrated approximately 2.7-fold higher ex vivo skin permeation compared to a free pirfenidone gel after 5 h. In lipopolysaccharide-stimulated RAW 264.7 macrophages, PFD-HSs exhibited high anti-inflammatory activity compared to free drug. Furthermore, in a bleomycin-induced scleroderma rat model, the formulation significantly reduces fibrotic and inflammatory markers (TNF-α, TGF-β, Col-1, α-SMA, and TIMP1), while significantly increases MMP2 expression. These biochemical improvements were further validated by histopathological findings. Pirfenidone-loaded hyaluosomes serve as a highly promising topical nanocarrier system, offering enhanced skin delivery and superior therapeutic outcomes for scleroderma management.