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Hyaluronic Acid-Decorated Liposomes as Innovative Targeted Delivery System for Lung Fibrotic Cells.

Laura Pandolfi1, Vanessa Frangipane2, Claudia Bocca3

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Molecules (Basel, Switzerland)
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Hyaluronic acid (HA) liposomes show promise for treating lung fibrosis in Collagen Tissue Disease-associated Interstitial Lung Fibrosis (CTD-ILDs) and Bronchiolitis Obliterans Syndrome (BOS). Higher molecular weight HA liposomes enhance targeting of CD44-expressing cells, with low pro-inflammatory activity.

Keywords:
Bronchiolitis Obliterans Syndromehyaluronic acidimmune cellsliposomeslung fibrosis

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Pulmonology

Background:

  • Collagen Tissue Disease-associated Interstitial Lung Fibrosis (CTD-ILDs) and Bronchiolitis Obliterans Syndrome (BOS) are severe fibrotic lung diseases.
  • Extracellular matrix deposition and fibro-proliferation characterize these conditions.
  • Hyaluronic acid (HA) and its receptor CD44 are implicated in the pathogenesis of CTD-ILDs and BOS.

Purpose of the Study:

  • To develop an inhalatory treatment using HA-liposomes for CTD-ILDs and BOS.
  • To evaluate the targeting efficiency and immune modulation of HA-liposomes in relevant cell models.

Main Methods:

  • Preparation and characterization of HA-liposomes with varying HA molecular weights.
  • Assessment of cellular uptake by CTD-ILD and BOS cells using flow cytometry and confocal microscopy.
  • Evaluation of immune modulation through RT-PCR and ELISA assays.

Main Results:

  • HA-liposomes were effectively internalized by CD44-expressing CTD-ILD and BOS cells, with increased uptake for higher HA molecular weights.
  • In THP-1 cells, HA-liposomes modulated specific cytokine transcripts but did not alter active pro-fibrotic cytokine release from monocytes.
  • Liposomes exhibited mild neutrophil activation, irrespective of HA presence, indicating low pro-inflammatory potential.

Conclusions:

  • HA-liposomes represent a potential inhalatory therapeutic strategy for lung fibrotic diseases like CTD-ILDs and BOS.
  • Higher molecular weight HA enhances liposome targeting efficiency towards CD44-expressing cells in these diseases.
  • The developed HA-liposomes demonstrate low pro-inflammatory activity, supporting their potential clinical application.