Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept
Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder associated with pulmonary emphysema and bronchiectasis. Its management currently consists of weekly infusions of plasma-purified human AAT, which poses several issues regarding plasma supplies, possible pathogen transmission, purification co...
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MDPI AG
2022-12-01
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Series: | Pharmaceutics |
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Online Access: | https://www.mdpi.com/1999-4923/14/12/2754 |
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author | Annalisa Bianchera Esraa’a Alomari Annalisa Michielon Gianluca Bazzoli Nicoletta Ronda Giovanni Pighini Ilaria Zanotti Carmine Giorgio Andrea Mozzarelli Ruggero Bettini Stefano Bruno |
author_facet | Annalisa Bianchera Esraa’a Alomari Annalisa Michielon Gianluca Bazzoli Nicoletta Ronda Giovanni Pighini Ilaria Zanotti Carmine Giorgio Andrea Mozzarelli Ruggero Bettini Stefano Bruno |
author_sort | Annalisa Bianchera |
collection | DOAJ |
description | Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder associated with pulmonary emphysema and bronchiectasis. Its management currently consists of weekly infusions of plasma-purified human AAT, which poses several issues regarding plasma supplies, possible pathogen transmission, purification costs, and parenteral administration. Here, we investigated an alternative administration strategy for augmentation therapy by combining recombinant expression of AAT in bacteria and the production of a respirable powder by spray drying. The same formulation approach was then applied to plasma-derived AAT for comparison. Purified, active, and endotoxin-free recombinant AAT was produced at high yields and formulated using L-leucine and mannitol as excipients after identifying compromise conditions for protein activity and good aerodynamic performances. An oxygen-free atmosphere, both during formulation and powder storage, slowed down methionine-specific oxidation and AAT inactivation. This work is the first peer-reviewed report of AAT formulated as a dry powder, which could represent an alternative to current treatments. |
first_indexed | 2024-03-09T15:58:55Z |
format | Article |
id | doaj.art-fe13ade3bfd143d499625d3914476803 |
institution | Directory Open Access Journal |
issn | 1999-4923 |
language | English |
last_indexed | 2024-03-09T15:58:55Z |
publishDate | 2022-12-01 |
publisher | MDPI AG |
record_format | Article |
series | Pharmaceutics |
spelling | doaj.art-fe13ade3bfd143d499625d39144768032023-11-24T17:21:27ZengMDPI AGPharmaceutics1999-49232022-12-011412275410.3390/pharmaceutics14122754Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of ConceptAnnalisa Bianchera0Esraa’a Alomari1Annalisa Michielon2Gianluca Bazzoli3Nicoletta Ronda4Giovanni Pighini5Ilaria Zanotti6Carmine Giorgio7Andrea Mozzarelli8Ruggero Bettini9Stefano Bruno10Department of Food and Drug, University of Parma, 43124 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyAlpha-1 antitrypsin (AAT) deficiency is a genetic disorder associated with pulmonary emphysema and bronchiectasis. Its management currently consists of weekly infusions of plasma-purified human AAT, which poses several issues regarding plasma supplies, possible pathogen transmission, purification costs, and parenteral administration. Here, we investigated an alternative administration strategy for augmentation therapy by combining recombinant expression of AAT in bacteria and the production of a respirable powder by spray drying. The same formulation approach was then applied to plasma-derived AAT for comparison. Purified, active, and endotoxin-free recombinant AAT was produced at high yields and formulated using L-leucine and mannitol as excipients after identifying compromise conditions for protein activity and good aerodynamic performances. An oxygen-free atmosphere, both during formulation and powder storage, slowed down methionine-specific oxidation and AAT inactivation. This work is the first peer-reviewed report of AAT formulated as a dry powder, which could represent an alternative to current treatments.https://www.mdpi.com/1999-4923/14/12/2754alpha-1 antitrypsinrecombinant proteinpulmonary drug deliveryinhalable dry powder |
spellingShingle | Annalisa Bianchera Esraa’a Alomari Annalisa Michielon Gianluca Bazzoli Nicoletta Ronda Giovanni Pighini Ilaria Zanotti Carmine Giorgio Andrea Mozzarelli Ruggero Bettini Stefano Bruno Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept Pharmaceutics alpha-1 antitrypsin recombinant protein pulmonary drug delivery inhalable dry powder |
title | Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept |
title_full | Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept |
title_fullStr | Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept |
title_full_unstemmed | Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept |
title_short | Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept |
title_sort | recombinant alpha 1 antitrypsin as dry powder for pulmonary administration a formulative proof of concept |
topic | alpha-1 antitrypsin recombinant protein pulmonary drug delivery inhalable dry powder |
url | https://www.mdpi.com/1999-4923/14/12/2754 |
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