Hyaluronic acid-decorated liposomes as innovative targeted delivery system for lung fibrotic cells

Laura Pandolfi, Vanessa Frangipane, Claudia Bocca, Alessandro Marengo, Erika Tarro Genta, Sara Bozzini, Monica Morosini, Maura D'Amato, Simone Vitulo, Manuela Monti, Giuditta Comolli, Maria Teresa Scupoli, Elias Fattal, Silvia Arpicco, Federica Meloni

Research output: Contribution to journalArticlepeer-review

Abstract

Collagen Tissue Disease-associated Interstitial Lung Fibrosis (CTD-ILDs) and Bronchiolitis Obliterans Syndrome (BOS) represent severe lung fibrogenic disorders, characterized by fibro-proliferation with uncontrolled extracellular matrix deposition. Hyaluronic acid (HA) plays a key role in fibrosis with its specific receptor, CD44, overexpressed by CTD-ILD and BOS cells. The aim is to use HA-liposomes to develop an inhalatory treatment for these diseases. Liposomes with HA of two molecular weights were prepared and characterized. Targeting efficiency was assessed toward CTD-ILD and BOS cells by flow cytometry and confocal microscopy and immune modulation by RT-PCR and ELISA techniques. HA-liposomes were internalized by CTD-ILD and BOS cells expressing CD44, and this effect increased with higher HA MW. In THP-1 cells, HA-liposomes decreased pro-inflammatory cytokines IL-1β, IL-12, and anti-fibrotic VEGF transcripts but increased TGF-β mRNA. However, upon analyzing TGF-β release from healthy donors-derived monocytes, we found liposomes did not alter the release of active pro-fibrotic cytokine. All liposomes induced mild activation of neutrophils regardless of the presence of HA. HA liposomes could be also applied for lung fibrotic diseases, being endowed with low pro-inflammatory activity, and results confirmed that higher MW HA are associated to an increased targeting efficiency for CD44 expressing LFs-derived from BOS and CTD-ILD patients.

Original languageEnglish
Article number3291
JournalMolecules
Volume24
Issue number18
DOIs
Publication statusPublished - Sep 10 2019

Keywords

  • Bronchiolitis obliterans syndrome
  • Hyaluronic acid
  • Immune cells
  • Liposomes
  • Lung fibrosis

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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