Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 552, Issue 1-2, Pages 67-75Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2018.09.045
Keywords
siRNA; Spray freeze drying; Next generation impactor; Pulmonary delivery; Gene silencing
Categories
Funding
- Health and Medical Research Fund, Hong Kong [HMRF 15140962]
- Research Grants Council, Hong Kong [GRF 17302815]
- National Natural Science Foundation of China, China [NSFC 81573373]
- HKU/Sydney Partnership Fund
Ask authors/readers for more resources
Spray freeze drying is an attractive technology to produce powder formulation for inhalation. It can be used to generate large porous particles which tend to aerosolize efficiently and do not aggregate readily. It also avoids material to be exposed to elevated temperature. In this study, we reported the use of two-fluid nozzle to produce spray freeze dried powder of small interfering RNA (siRNA). The effect of atomization gas flow rate and liquid feed rate were inspected initially using herring sperm DNA (hsDNA) as nucleic acid model. The atomization gas flow rate was found to have a major impact on the aerosol properties. The higher the atomization gas flow rate, the smaller the particle size, the higher the fine particle fraction (FPF). In contrast, the liquid feed rate had very minor effect. Subsequently, spray freeze dried siRNA powder was produced at various atomization gas flow rates. The particles produced were highly porous as examined with the scanning electron microscopy, and the structural integrity of the siRNA was demonstrated with gel electrophoresis. The gene-silencing effect of the siRNA was also successfully preserved in vitro. The best performing siRNA formulation was prepared at the highest atomization gas flow rate investigated with a moderate FPF of 30%. However, this was significantly lower than that obtained with the corresponding hsDNA counterparts (FPF similar to 57%). A direct comparison between the hsDNA and siRNA formulations revealed that the former exhibited a lower density, hence a smaller aerodynamic diameter despite similar geometric size.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available