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Kotta S, Aldawsari HM, Badr-Eldin SM, et al. Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics. Pharmaceutics. 2021;13(11)doi: 10.3390/pharmaceutics13111851.
Kotta, S., Aldawsari, H. M., Badr-Eldin, S. M., Binmahfouz, L. S., Bakhaidar, R. B., Sreeharsha, N., Nair, A. B., & Ramnarayanan, C. (2021). Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics. Pharmaceutics, 13(11), . https://doi.org/10.3390/pharmaceutics13111851
Kotta, Sabna, et al. "Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics." Pharmaceutics vol. 13,11 (2021). doi: https://doi.org/10.3390/pharmaceutics13111851
Kotta S, Aldawsari HM, Badr-Eldin SM, Binmahfouz LS, Bakhaidar RB, Sreeharsha N, Nair AB, Ramnarayanan C. Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics. Pharmaceutics. 2021 Nov 03;13(11). doi: 10.3390/pharmaceutics13111851. PMID: 34834265; PMCID: PMC8625129.
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Pharmaceutics. 2021 Nov 03;13(11). doi: 10.3390/pharmaceutics13111851.

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

Pharmaceutics

Sabna Kotta, Hibah Mubarak Aldawsari, Shaimaa M Badr-Eldin, Lenah S Binmahfouz, Rana Bakur Bakhaidar, Nagaraja Sreeharsha, Anroop B Nair, Chandramouli Ramnarayanan

Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  2. Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  4. Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
  5. Department of Pharmaceutics, Vidya Siri College of Pharmacy, Off Sarjapura Road, Bangalore 560035, India.
  6. Department of Pharmaceutical Chemistry, Vidya Siri College of Pharmacy, Off Sarjapura Road, Bangalore 560035, India.
  7. Global Technical Enablement JMP Division, SAS India Pvt. Ltd., Lavelle Road, Bengaluru 560025, India.

PMID: 34834265 PMCID: PMC8625129 DOI: 10.3390/pharmaceutics13111851

Abstract

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.

Keywords: aerosol; bleomycin; liposomes; naringin; pulmonary fibrosis

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