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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/14/7743 |
| _version_ | 1797526834098733056 |
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| author | Laura Pandolfi Alessandro Marengo Kamila Bohne Japiassu Vanessa Frangipane Nicolas Tsapis Valeria Bincoletto Veronica Codullo Sara Bozzini Monica Morosini Sara Lettieri Valentina Vertui Davide Piloni Silvia Arpicco Elias Fattal Federica Meloni |
| author_facet | Laura Pandolfi Alessandro Marengo Kamila Bohne Japiassu Vanessa Frangipane Nicolas Tsapis Valeria Bincoletto Veronica Codullo Sara Bozzini Monica Morosini Sara Lettieri Valentina Vertui Davide Piloni Silvia Arpicco Elias Fattal Federica Meloni |
| author_sort | Laura Pandolfi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T09:35:56Z |
| format | Article |
| id | doaj.art-08120ae64af54263a4e38bbbb455354b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:35:56Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-08120ae64af54263a4e38bbbb455354b2023-11-22T04:03:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214774310.3390/ijms22147743Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung FibrosisLaura Pandolfi0Alessandro Marengo1Kamila Bohne Japiassu2Vanessa Frangipane3Nicolas Tsapis4Valeria Bincoletto5Veronica Codullo6Sara Bozzini7Monica Morosini8Sara Lettieri9Valentina Vertui10Davide Piloni11Silvia Arpicco12Elias Fattal13Federica Meloni14Research Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, ItalyInstitut Galien Paris-Saclay, CNRS, Université Paris-Saclay, Châtenay-Malabry, 92296 Paris, FranceInstitut Galien Paris-Saclay, CNRS, Université Paris-Saclay, Châtenay-Malabry, 92296 Paris, FranceResearch Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, ItalyInstitut Galien Paris-Saclay, CNRS, Université Paris-Saclay, Châtenay-Malabry, 92296 Paris, FranceDepartment of Drug Science and Technology, University of Turin, 10125 Turin, ItalyUnit of Rheumatology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, ItalyResearch Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, ItalyResearch Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, ItalyPneumology Unit, IRCCS Policlinico San Matteo Foundation, University of Pavia, 27100 Pavia, ItalyPneumology Unit, IRCCS Policlinico San Matteo Foundation, University of Pavia, 27100 Pavia, ItalyPneumology Unit, IRCCS Policlinico San Matteo Foundation, University of Pavia, 27100 Pavia, ItalyDepartment of Drug Science and Technology, University of Turin, 10125 Turin, ItalyInstitut Galien Paris-Saclay, CNRS, Université Paris-Saclay, Châtenay-Malabry, 92296 Paris, FranceResearch Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, ItalyChronic 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.https://www.mdpi.com/1422-0067/22/14/7743liposomeshyaluronic acideverolimuslung diseases |
| spellingShingle | Laura Pandolfi Alessandro Marengo Kamila Bohne Japiassu Vanessa Frangipane Nicolas Tsapis Valeria Bincoletto Veronica Codullo Sara Bozzini Monica Morosini Sara Lettieri Valentina Vertui Davide Piloni Silvia Arpicco Elias Fattal Federica Meloni Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis International Journal of Molecular Sciences liposomes hyaluronic acid everolimus lung diseases |
| title | Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis |
| title_full | Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis |
| title_fullStr | Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis |
| title_full_unstemmed | Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis |
| title_short | Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis |
| title_sort | liposomes loaded with everolimus and coated with hyaluronic acid a promising approach for lung fibrosis |
| topic | liposomes hyaluronic acid everolimus lung diseases |
| url | https://www.mdpi.com/1422-0067/22/14/7743 |
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