Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics

Excessive architectural re-modeling of tissues in pulmonary fibrosis due to proliferation of myofibroblasts and deposition of extracellular matrix adversely affects the elasticity of the alveoli and lung function. Progressively destructive chronic inflammatory disease, therefore, necessitates safe a...

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Autores principales:	Sabna Kotta, Hibah Mubarak Aldawsari, Shaimaa M. Badr-Eldin, Lenah S. Binmahfouz, Rana Bakur Bakhaidar, Nagaraja Sreeharsha, Anroop B. Nair, Chandramouli Ramnarayanan
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	pulmonary fibrosis naringin bleomycin liposomes aerosol Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/cac88cef30194690be98c6417e27dc3f
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spelling	oai:doaj.org-article:cac88cef30194690be98c6417e27dc3f2021-11-25T18:41:09ZAerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics10.3390/pharmaceutics131118511999-4923https://doaj.org/article/cac88cef30194690be98c6417e27dc3f2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1851https://doaj.org/toc/1999-4923Excessive architectural re-modeling of tissues in pulmonary fibrosis due to proliferation of myofibroblasts and deposition of extracellular matrix adversely affects the elasticity of the alveoli and lung function. Progressively destructive chronic inflammatory disease, therefore, necessitates safe and effective non-invasive airway delivery that can reach deep alveoli, restore the surfactant function and reduce oxidative stress. We designed an endogenous surfactant-based liposomal delivery system of naringin to be delivered as an aerosol that supports pulmonary mechanics for the management of pulmonary fibrosis. Phosphatidylcholine-based liposomes showed 91.5 ± 2.4% encapsulation of naringin, with a mean size of 171.4 ± 5.8 nm and zeta potential of −15.5 ± 1.3 mV. Liposomes with the unilamellar structure were found to be spherical and homogeneous in shape using electron microscope imaging. The formulation showed surface tension of 32.6 ± 0.96 mN/m and was able to maintain airway patency of 97 ± 2.5% for a 120 s test period ensuring the effective opening of lung capillaries and deep lung delivery. In vitro lung deposition utilizing Twin Stage Impinger showed 79 ± 1.5% deposition in lower airways, and Anderson Cascade Impactor deposition revealed a mass median aerodynamic diameter of 2.35 ± 1.02 μm for the aerosolized formulation. In vivo efficacy of the developed formulation was analyzed in bleomycin-induced lung fibrosis model in rats after administration by the inhalation route. Lactate dehydrogenase activity, total protein content, and inflammatory cell infiltration in broncho-alveolar lavage fluid were substantially reduced by liposomal naringin. Oxidative stress was minimized as observed from levels of antioxidant enzymes. Masson’s Trichrome staining of lung tissue revealed significant amelioration of histological changes and lesser deposition of collagen. Overall results indicated the therapeutic potential of the developed non-invasive aerosol formulation for the effective management of pulmonary fibrosis.Sabna KottaHibah Mubarak AldawsariShaimaa M. Badr-EldinLenah S. BinmahfouzRana Bakur BakhaidarNagaraja SreeharshaAnroop B. NairChandramouli RamnarayananMDPI AGarticlepulmonary fibrosisnaringinbleomycinliposomesaerosolPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1851, p 1851 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pulmonary fibrosis naringin bleomycin liposomes aerosol Pharmacy and materia medica RS1-441
spellingShingle	pulmonary fibrosis naringin bleomycin liposomes aerosol Pharmacy and materia medica RS1-441 Sabna Kotta Hibah Mubarak Aldawsari Shaimaa M. Badr-Eldin Lenah S. Binmahfouz Rana Bakur Bakhaidar Nagaraja Sreeharsha Anroop B. Nair Chandramouli Ramnarayanan Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics
description	Excessive architectural re-modeling of tissues in pulmonary fibrosis due to proliferation of myofibroblasts and deposition of extracellular matrix adversely affects the elasticity of the alveoli and lung function. Progressively destructive chronic inflammatory disease, therefore, necessitates safe and effective non-invasive airway delivery that can reach deep alveoli, restore the surfactant function and reduce oxidative stress. We designed an endogenous surfactant-based liposomal delivery system of naringin to be delivered as an aerosol that supports pulmonary mechanics for the management of pulmonary fibrosis. Phosphatidylcholine-based liposomes showed 91.5 ± 2.4% encapsulation of naringin, with a mean size of 171.4 ± 5.8 nm and zeta potential of −15.5 ± 1.3 mV. Liposomes with the unilamellar structure were found to be spherical and homogeneous in shape using electron microscope imaging. The formulation showed surface tension of 32.6 ± 0.96 mN/m and was able to maintain airway patency of 97 ± 2.5% for a 120 s test period ensuring the effective opening of lung capillaries and deep lung delivery. In vitro lung deposition utilizing Twin Stage Impinger showed 79 ± 1.5% deposition in lower airways, and Anderson Cascade Impactor deposition revealed a mass median aerodynamic diameter of 2.35 ± 1.02 μm for the aerosolized formulation. In vivo efficacy of the developed formulation was analyzed in bleomycin-induced lung fibrosis model in rats after administration by the inhalation route. Lactate dehydrogenase activity, total protein content, and inflammatory cell infiltration in broncho-alveolar lavage fluid were substantially reduced by liposomal naringin. Oxidative stress was minimized as observed from levels of antioxidant enzymes. Masson’s Trichrome staining of lung tissue revealed significant amelioration of histological changes and lesser deposition of collagen. Overall results indicated the therapeutic potential of the developed non-invasive aerosol formulation for the effective management of pulmonary fibrosis.
format	article
author	Sabna Kotta Hibah Mubarak Aldawsari Shaimaa M. Badr-Eldin Lenah S. Binmahfouz Rana Bakur Bakhaidar Nagaraja Sreeharsha Anroop B. Nair Chandramouli Ramnarayanan
author_facet	Sabna Kotta Hibah Mubarak Aldawsari Shaimaa M. Badr-Eldin Lenah S. Binmahfouz Rana Bakur Bakhaidar Nagaraja Sreeharsha Anroop B. Nair Chandramouli Ramnarayanan
author_sort	Sabna Kotta
title	Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics
title_short	Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics
title_full	Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics
title_fullStr	Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics
title_full_unstemmed	Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics
title_sort	aerosol delivery of surfactant liposomes for management of pulmonary fibrosis: an approach supporting pulmonary mechanics
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cac88cef30194690be98c6417e27dc3f
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Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics

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