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Volume 22
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10.3390/ijms22147743
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Article

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

by
Laura Pandolfi
1,*,
Alessandro Marengo
2,
Kamila Bohne Japiassu
2,
Vanessa Frangipane
1,
Nicolas Tsapis
2,
Valeria Bincoletto
3,
Veronica Codullo
4,
Sara Bozzini
1,
Monica Morosini
1,
Sara Lettieri
5,
Valentina Vertui
5,
Davide Piloni
5,
Silvia Arpicco
3,
Elias Fattal
2 and
Federica Meloni
1,5
1
Research Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy
2
Institut Galien Paris-Saclay, CNRS, Université Paris-Saclay, Châtenay-Malabry, 92296 Paris, France
3
Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy
4
Unit of Rheumatology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy
5
Pneumology Unit, IRCCS Policlinico San Matteo Foundation, University of Pavia, 27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(14), 7743; https://doi.org/10.3390/ijms22147743
Submission received: 1 June 2021 / Revised: 6 July 2021 / Accepted: 14 July 2021 / Published: 20 July 2021
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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Abstract

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.
Keywords: liposomes; hyaluronic acid; everolimus; lung diseases liposomes; hyaluronic acid; everolimus; lung diseases

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MDPI and ACS Style

Pandolfi, L.; Marengo, A.; Japiassu, K.B.; Frangipane, V.; Tsapis, N.; Bincoletto, V.; Codullo, V.; Bozzini, S.; Morosini, M.; Lettieri, S.; et al. Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis. Int. J. Mol. Sci. 2021, 22, 7743. https://doi.org/10.3390/ijms22147743

AMA Style

Pandolfi L, Marengo A, Japiassu KB, Frangipane V, Tsapis N, Bincoletto V, Codullo V, Bozzini S, Morosini M, Lettieri S, et al. Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis. International Journal of Molecular Sciences. 2021; 22(14):7743. https://doi.org/10.3390/ijms22147743

Chicago/Turabian Style

Pandolfi, Laura, Alessandro Marengo, Kamila Bohne Japiassu, Vanessa Frangipane, Nicolas Tsapis, Valeria Bincoletto, Veronica Codullo, Sara Bozzini, Monica Morosini, Sara Lettieri, and et al. 2021. "Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis" International Journal of Molecular Sciences 22, no. 14: 7743. https://doi.org/10.3390/ijms22147743

APA Style

Pandolfi, L., Marengo, A., Japiassu, K. B., Frangipane, V., Tsapis, N., Bincoletto, V., Codullo, V., Bozzini, S., Morosini, M., Lettieri, S., Vertui, V., Piloni, D., Arpicco, S., Fattal, E., & Meloni, F. (2021). Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis. International Journal of Molecular Sciences, 22(14), 7743. https://doi.org/10.3390/ijms22147743

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