Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis

Chronic lung allograft dysfunction (CLAD) and interstitial lung disease associated with collagen tissue diseases (CTD-ILD) are two end-stage lung disorders in which different chronic triggers induce activation of myo-/fibroblasts (LFs). Everolimus, an mTOR inhibitor, can be adopted as a potential st...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-07, Vol.22 (14), p.7743
Main Authors: Pandolfi, Laura, Marengo, Alessandro, Japiassu, Kamila Bohne, Frangipane, Vanessa, Tsapis, Nicolas, Bincoletto, Valeria, Codullo, Veronica, Bozzini, Sara, Morosini, Monica, Lettieri, Sara, Vertui, Valentina, Piloni, Davide, Arpicco, Silvia, Fattal, Elias, Meloni, Federica
Format: Article
Language:English
Subjects:
Alveoli
CD44 antigen
Cell cycle
Cell growth
Collagen
Efficiency
everolimus
Fibroblasts
Fibrosis
Galenic pharmacology
Human health and pathology
Hyaluronic acid
Immune system
Inflammation
Life Sciences
Lipids
Liposomes
Lung diseases
Lymphocytes
Macrophages
Molecular weight
Nanoparticles
Nanotechnology
NMR
Nuclear magnetic resonance
Peripheral blood
Pharmaceutical sciences
Pulmonology and respiratory tract
Side effects
TOR protein
Transplants & implants
Xenografts
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Summary:Chronic lung allograft dysfunction (CLAD) and interstitial lung disease associated with collagen tissue diseases (CTD-ILD) are two end-stage lung disorders in which different chronic triggers induce activation of myo-/fibroblasts (LFs). Everolimus, an mTOR inhibitor, can be adopted as a potential strategy for CLAD and CTD-ILD, however it exerts important side effects. This study aims to exploit nanomedicine to reduce everolimus side effects encapsulating it inside liposomes targeted against LFs, expressing a high rate of CD44. PEGylated liposomes were modified with high molecular weight hyaluronic acid and loaded with everolimus (PEG-LIP(ev)-HA400kDa). Liposomes were tested by in vitro experiments using LFs derived from broncholveolar lavage (BAL) of patients affected by CLAD and CTD-ILD, and on alveolar macrophages (AM) and lymphocytes isolated, respectively, from BAL and peripheral blood. PEG-LIP-HA400kDa demonstrated to be specific for LFs, but not for CD44-negative cells, and after loading everolimus, PEG-LIP(ev)-HA400kDa were able to arrest cell cycle arrest and to decrease phospho-mTOR level. PEG-LIP(ev)-HA400kDa showed anti-inflammatory effect on immune cells. This study opens the possibility to use everolimus in lung fibrotic diseases, demonstrating that our lipids-based vehicles can vehicle everolimus inside cells exerting the same drug molecular effect, not only in LFs, but also in immune cells.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22147743