Cystic fibrosis, a genetic disorder affecting multiple organs in the body, including the lungs, remains a significant threat to patients due to inadequate treatment options. Treatment includes aerosolized deoxyribonuclease I which bolsters pulmonary function and improves affected patient condition. However, taking the liquid formulations requires prolonged inhalation times and nebulization equipment. Conversely, dry powder inhalers are handheld devices, delivering fine particles deep into the lung on a single inhalation. Dry formulations may be enhanced through the use of mesoporous silica particles which have an optimal size for inhalation, are light in weight and have a large surface area. Loading deoxyribonuclease I into mesoporous silica particles could potentially improve drug delivery to cystic fibrosis patients with reduced administration frequency when taken with dry powder inhalers. The incorporation of buffers into this system is crucial for ensuring efficient drug loading and stability at the biointerface during dry powder preparation. Thus, the objective of this project was to ascertain the most suitable buffer composition for loading deoxyribonuclease I into mesoporous silica particles. Protein size and activity were evaluated in different buffers prior to adsorption. Subsequently, dry formulations were prepared by freeze drying, and studied by thermogravimetric analysis and dynamic vapour sorption. Cumulative release analysis in simulated lung fluid was performed, followed by released protein enzymatic activity evaluation. Findings indicated the necessity of incorporating Ca2+ into buffers to increase protein loading efficiency and stability in dry formulations. Highest level of adsorption, and adequate remaining deoxyribonuclease I activity was observed in formulations prepared with calcium doped mesoporous silica particles in pH 5.0 50 mM sodium acetate buffer with added 5 mM CaCl2.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:mau-68090 |
| Date | January 2024 |
| Creators | Startaite, Lauryna |
| Publisher | Malmö universitet, Institutionen för biomedicinsk vetenskap (BMV) |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Student thesis, info:eu-repo/semantics/bachelorThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
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