Inhalers are designed to safely and efficiently deliver drug formulations to the pulmonary epithelium, where the drug can then be absorbed into the local tissue or the systemic circulation for therapeutic action. Common inhalational products include inhalation solutions, pressurized metered-dose inhalers, and dry powder inhalers (DPIs). While each has certain advantages for the delivery of drugs, DPIs are usually the first choice for inhalational biopharmaceuticals development.
In this study, we developed a protein DPI formulation by electrospinning (ES) a polymer solution of drug into 200-1,000 nm diameter nanofiber mats. The polymer solution is collected through electrostatic attraction, resulting in an exceptionally high recovery rate compared with spray drying. Additionally, as the solvent evaporates at room temperature upon reaching the collector, the ES method can solidify a polymer solution without the need for heat. In the current study, mannitol (Man) was added to reduce the milling time required for nanofiber mats and produce a DPI suitable for delivery of proteins. We evaluated in vitro aerosol performance and enzymatic activity as well as in vitro and in vivo toxicity.
The dry powders were produced by milling nanofiber mats, and those containing Man formed only weak aggregates after brief milling and demonstrated superior aerosol performance. Morphological observations at each stage of an eight-stage Andersen cascade impactor revealed that the enhanced aerosol performance of milled nanofiber mats containing Man can be attributed to detachment of aggregates during inhalation. Furthermore, the protein enzymatic activity of the milled nanofiber mats surpassed that of a nebulized solution. Furthermore, single inhalation induced no significant lung tissue damage as evidenced by lactate dehydrogenase activity assays of mouse bronchoalveolar lavage fluid.
This study introduces a novel electrospinning-based DPI preparation method that eliminates the need for heating and is particularly suitable for inhalation formulations of high molecular weight drugs such as proteins.
Article information
Journal : International Journal of Pharmaceutics
Journal title : Cryomilled electrospun nanofiber mats containing D-mannitol exhibit suitable for aerosol delivery of proteins
Authors : Takaaki Ito, Shintaro Tamashiro, Hiroki Okuda , Eriko Yamazoe , Kohei Tahara
DOI: 10.1016/j.ijpharm.2024.124425
Lab
Laboratory of Pharmaceutical Engineering
https://gpu-seizai.jp