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Open AccessArticle

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

1
Research Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy
2
Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy
3
Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy
4
Laboratory of Biotechnology, Center of Regenerative Medicine Research, IRCCS San Matteo Foundation, 27100 Pavia, Italy
5
Experimental Research Laboratories, Biotechnology Area, IRCCS San Matteo Foundation, 27100 Pavia, Italy
6
Molecular Virology Unit, Microbiology and Virology Department, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy
7
Research Center LURM, Interdepartmental Laboratory of Medical Research, University of Verona, 37134 Verona, Italy
8
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37129 Verona, Italy
9
Institut Galien Paris-Sud, CNRS, Université Paris-Sud, Université Paris-Saclay, 922996 Châtenay-Malabry, France
10
Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Derek J. McPhee
Molecules 2019, 24(18), 3291; https://doi.org/10.3390/molecules24183291
Received: 16 August 2019 / Revised: 5 September 2019 / Accepted: 7 September 2019 / Published: 10 September 2019
(This article belongs to the Special Issue Hyaluronic Acid and its Derivatives for Biomedical Applications)
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. View Full-Text
Keywords: liposomes; Bronchiolitis Obliterans Syndrome; lung fibrosis; hyaluronic acid; immune cells liposomes; Bronchiolitis Obliterans Syndrome; lung fibrosis; hyaluronic acid; immune cells
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MDPI and ACS Style

Pandolfi, L.; Frangipane, V.; Bocca, C.; Marengo, A.; Tarro Genta, E.; Bozzini, S.; Morosini, M.; D’Amato, M.; Vitulo, S.; Monti, M.; Comolli, G.; Scupoli, M.T.; Fattal, E.; Arpicco, S.; Meloni, F. Hyaluronic Acid–Decorated Liposomes as Innovative Targeted Delivery System for Lung Fibrotic Cells. Molecules 2019, 24, 3291.

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