Antifibrotic Activity of Conjugates Based on Amphiphilic Pluronic F68 and Hydrophobic Pluronic L31 with Hyaluronate-Endo-β-N-Acetylhexosaminidase in Pulmonary Fibrosis

Скурихин, Е. Г.; Reztsova, A. M.; Ермакова, Н. Н.; Krupin, V. A.; Першина, О. В.; Khmelevskaya, E. S.; Artamonov, Andrey; Bekarev, A. A.; Мадонов, П. Г.; Kinsht, D. N.; Reykhard, D. V.; Goldberg, V. Е.; Дыгай, А. М.

doi:10.1007/s10517-014-2478-0

Cited by 3 publications

(1 citation statement)

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“…Indeed, such structures are have been used for targeted therapy [ 16 , 17 , 18 , 19 , 20 , 21 ]. We have previously studied the effects of conjugates of pluronics with a predominance of hydrophobic properties and amphiphilic properties with hyaluronidase [ 22 ]. Stable antifibrotic effects were mediated by a conjugate based on hydrophobic Pluronic L31 with hyaluronidase (poloxamer-hyaluronidase or pHD).…”

Section: Introductionmentioning

confidence: 99%

Micellar Hyaluronidase and Spiperone as a Potential Treatment for Pulmonary Fibrosis

Скурихин

Мадонов²,

Першина

et al. 2021

IJMS

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Concentration of hyaluronic acid (HA) in the lungs increases in idiopathic pulmonary fibrosis (IPF). HA is involved in the organization of fibrin, fibronectin, and collagen. HA has been proposed to be a biomarker of fibrosis and a potential target for antifibrotic therapy. Hyaluronidase (HD) breaks down HA into fragments, but is a subject of rapid hydrolysis. A conjugate of poloxamer hyaluronidase (pHD) was prepared using protein immobilization with ionizing radiation. In a model of bleomycin-induced pulmonary fibrosis, pHD decreased the level of tissue IL-1β and TGF-β, prevented the infiltration of the lung parenchyma by CD16+ cells, and reduced perivascular and peribronchial inflammation. Simultaneously, a decrease in the concentrations of HA, hydroxyproline, collagen 1, total soluble collagen, and the area of connective tissue in the lungs was observed. The effects of pHD were significantly stronger compared to native HD which can be attributed to the higher stability of pHD. Additional spiperone administration increased the anti-inflammatory and antifibrotic effects of pHD and accelerated the regeneration of the damaged lung. The potentiating effects of spiperone can be explained by the disruption of the dopamine-induced mobilization and migration of fibroblast progenitor cells into the lungs and differentiation of lung mesenchymal stem cells (MSC) into cells of stromal lines. Thus, a combination of pHD and spiperone may represent a promising approach for the treatment of IPF and lung regeneration.

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