Nebulization may be an effective way to administer alpha-1 antitrypsin (AAT) directly to the lungs of patients with alpha-1 antitrypsin deficiency (AATD), according to a study published in Drug Delivery and Translational Research.
The researchers compared the in vitro effectiveness of 2 commercially available inhalation systems: a jet and a mesh vibrating system, both used with a commercial preparation of AAT for infusion.
They investigated various indicators of aerosolization performance: mass distribution, respirable fraction, drug delivery efficiency, and the activity and aggregation state of AAT upon in vitro nebulization.
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According to the results, the 2 nebulizers showed similar effectiveness. However, the use of mesh nebulizers resulted in higher lung delivery of the administered dose. AAT activity was preserved with both devices, and there were no signs of aggregation or changes in the protein conformation.
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“This allows us to conclude that nebulization of a solution, even though not optimized for this administration way, may represent a suitable administration strategy in 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,” Bianchera and colleagues concluded.
The standard approach to AATD treatment involves weekly, slow intravenous infusions of AAT purified from human plasma to restore the protective plasma level of about 60 mg/dL. Aside from the high costs of infusions, this treatment must be administered by healthcare staff in a medical setting. Moreover, only 3% of intravenously administered AAT may actually reach the patient’s lung epithelium.
Reference
Bianchera A, Vilardo V, Giaccari R, et al. Nebulizers effectiveness on pulmonary delivery of alpha-1 antitrypsin. Drug Deliv Transl Res. Published online April 25, 2023. doi:10.1007/s13346-023-01346-3
