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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/13/11/1851 |
| _version_ | 1797508823118774272 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:09:20Z |
| format | Article |
| id | doaj.art-cac88cef30194690be98c6417e27dc3f |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T05:09:20Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-cac88cef30194690be98c6417e27dc3f2023-11-23T00:58:34ZengMDPI AGPharmaceutics1999-49232021-11-011311185110.3390/pharmaceutics13111851Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary MechanicsSabna Kotta0Hibah Mubarak Aldawsari1Shaimaa M. Badr-Eldin2Lenah S. Binmahfouz3Rana Bakur Bakhaidar4Nagaraja Sreeharsha5Anroop B. Nair6Chandramouli Ramnarayanan7Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Vidya Siri College of Pharmacy, Off Sarjapura Road, Bangalore 560035, IndiaExcessive 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.https://www.mdpi.com/1999-4923/13/11/1851pulmonary fibrosisnaringinbleomycinliposomesaerosol |
| spellingShingle | 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 Pharmaceutics pulmonary fibrosis naringin bleomycin liposomes aerosol |
| title | 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_short | 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 |
| topic | pulmonary fibrosis naringin bleomycin liposomes aerosol |
| url | https://www.mdpi.com/1999-4923/13/11/1851 |
| work_keys_str_mv | AT sabnakotta aerosoldeliveryofsurfactantliposomesformanagementofpulmonaryfibrosisanapproachsupportingpulmonarymechanics AT hibahmubarakaldawsari aerosoldeliveryofsurfactantliposomesformanagementofpulmonaryfibrosisanapproachsupportingpulmonarymechanics AT shaimaambadreldin aerosoldeliveryofsurfactantliposomesformanagementofpulmonaryfibrosisanapproachsupportingpulmonarymechanics AT lenahsbinmahfouz aerosoldeliveryofsurfactantliposomesformanagementofpulmonaryfibrosisanapproachsupportingpulmonarymechanics AT ranabakurbakhaidar aerosoldeliveryofsurfactantliposomesformanagementofpulmonaryfibrosisanapproachsupportingpulmonarymechanics AT nagarajasreeharsha aerosoldeliveryofsurfactantliposomesformanagementofpulmonaryfibrosisanapproachsupportingpulmonarymechanics AT anroopbnair aerosoldeliveryofsurfactantliposomesformanagementofpulmonaryfibrosisanapproachsupportingpulmonarymechanics AT chandramouliramnarayanan aerosoldeliveryofsurfactantliposomesformanagementofpulmonaryfibrosisanapproachsupportingpulmonarymechanics |