Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept

Bianchera, Annalisa; Alomari, Esra'a; Michielon, Annalisa; Bazzoli, Gianluca; Ronda, Nicoletta; Pighini, Giovanni; Zanotti, Ilaria; Giorgio, Carmine; Mozzarelli, Andrea; Bettini, Ruggero; Bruno, Stefano

doi:10.3390/pharmaceutics14122754

Cited by 4 publications

(5 citation statements)

References 61 publications

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“…The second reason is that the use of an impinger rather than an impactor could reduce the interferences in the protein state due to prolonged exposition to air and, specifically for NGI, to the contact with the metal components or, in DD/DDR tests, to the recovery from filters. DLS analysis of samples collected in impingement chambers indicated that, right after dissolution, the AAT solution presented a single population of macromolecules having a hydrodynamic diameter of 7 nm, broadly consistent with previous reports on monomeric, monodispersed AAT [23,41]. The graph in Fig.…”

Section: Evaluation Of Aat Aggregation Upon Nebulizationsupporting

confidence: 90%

“…The samples deriving from DD/DDR tests or NGI tests were snap-frozen in liquid nitrogen and then stored at −80 °C to prevent activity loss over time [ 23 ]. They were then thawed immediately before the activity assays were performed.…”

Section: Methodsmentioning

confidence: 99%

“…Protein precipitation was assessed by SDS-PAGE as previously described [ 23 ]. All the measurements were carried out in replicate.…”

Section: Methodsmentioning

confidence: 99%

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Nebulizers effectiveness on pulmonary delivery of alpha-1 antitrypsin

Bianchera

Vilardo

Giaccari

et al. 2023

Drug Deliv. and Transl. Res.

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The nebulization of alpha-1 antitrypsin (AAT) for its administration to the lung could be an interesting alternative to parenteral infusion for patients suffering from AAT genetic deficiency (AATD). In the case of protein therapeutics, the effect of the nebulization mode and rate on protein conformation and activity must be carefully considered. In this paper two types of nebulizers, i.e., a jet and a mesh vibrating system, were used to nebulize a commercial preparation of AAT for infusion and compared. The aerosolization performance, in terms of mass distribution, respirable fraction, and drug delivery efficiency, as well as the activity and aggregation state of AAT upon in vitro nebulization were investigated. The two nebulizers demonstrated equivalent aerosolization performances, but the mesh nebulizer provided a higher efficiency in the delivery of the dose. The activity of the protein was acceptably preserved by both nebulizers and no aggregation or changes in its conformation were identified. This suggests that nebulization of AAT represents a suitable administration strategy ready to be translated to the clinical practice for delivering the protein directly to the lungs in AATD patients, either as a support therapy to parenteral administration or for subjects with a precocious diagnosis, to prevent the onset of pulmonary symptoms. Graphical Abstract

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Section: Evaluation Of Aat Aggregation Upon Nebulizationsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

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Nebulizers effectiveness on pulmonary delivery of alpha-1 antitrypsin

Bianchera

Vilardo

Giaccari

et al. 2023

Drug Deliv. and Transl. Res.

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“…Finally, we have only analyzed inhaled long-acting bronchodilators and ICS. Other inhaled drugs such as antibiotics [ 25 ] and, in the near future, other potential drugs that will be administered in inhaled form [ 26 ] have not been considered in this article, nor has nebulized therapy [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Different Doses in Inhaled Therapy: A Comprehensive Analysis

Lopez-Campos,

Reinoso-Arija,

Ferrer Galván

et al. 2023

Pharmaceutics

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Background. Currently, there is a considerable degree of confusion over the dosage of inhaled medications. Here, we carried out a review of all the doses used for the devices used in inhalation therapy. Methods. We first performed a systematic search of the different inhalation devices included on the July 2023 Spanish Ministry of Health Billing List. We then consulted the Spanish Agency for Medicines and Health Products to find the updated official label and to obtain the information on the exact composition. Results. We identified 90 unique products, of which 22 were long-acting bronchodilators (and combinations thereof) and 68 were products containing inhaled corticosteroids (ICS). Overall, 10 products with bronchodilators and 40 with ICS were marketed with the metered dose, while 11 with bronchodilators and 28 with ICS were marketed with the delivered dose. In addition, in some bronchodilators, the drug was referred to as a type of salt, whereas in others the information referred to the drug itself. Conclusions. Our data show that for each inhaled drug there may be up to four different doses and that the marketed name may refer to any of these. Clinicians must be aware of these different dosages when prescribing inhaled medications.

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“…Alternatively, inhaled therapies directed at the overabundance of NE may also be worth exploring in further detail, e.g. alpha-1 antitrypsin augmentation therapy [ 105 ]. Alternatives to antibiotics include inhaled immunoglobulin.…”

Section: Perspective and Future Therapiesmentioning

confidence: 99%

Basic, translational and clinical aspects of bronchiectasis in adults

Chalmers¹,

Elborn²,

Greene³

2023

Eur Respir Rev

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Bronchiectasis is a common progressive respiratory disease with recognisable radiological abnormalities and a clinical syndrome of cough, sputum production and recurrent respiratory infections. Inflammatory cell infiltration into the lung, in particular neutrophils, is central to the pathophysiology of bronchiectasis. Herein we explore the roles and relationships between infection, inflammation and mucociliary clearance dysfunction in the establishment and progression of bronchiectasis. Microbial and host-mediated damage are important processes underpinning bronchiectasis and the relative contribution of proteases, cytokines and inflammatory mediators to the propagation of inflammation is presented. We also discuss the emerging concept of inflammatory endotypes, defined by the presence of neutrophilic and eosinophilic inflammation, and explore the role of inflammation as a treatable trait. Current treatment for bronchiectasis focuses on treatment of underlying causes, enhancing mucociliary clearance, controlling infection and preventing and treating complications. Data on airway clearance approachesviaexercise and mucoactive drugs, pharmacotherapy with macrolides to decrease exacerbations and the usefulness of inhaled antibiotics and bronchodilators are discussed, finishing with a look to the future where new therapies targeting host-mediated immune dysfunction hold promise.

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Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept

Cited by 4 publications

References 61 publications

Nebulizers effectiveness on pulmonary delivery of alpha-1 antitrypsin

Nebulizers effectiveness on pulmonary delivery of alpha-1 antitrypsin

Evaluation of Different Doses in Inhaled Therapy: A Comprehensive Analysis

Basic, translational and clinical aspects of bronchiectasis in adults

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