Abstract:
:Systems for delivering nucleic acids are now fundamental technologies for realizing personalized medicine. Among the various nucleic acid delivery systems that are currently available, lipid-nanoparticles (LNPs) that contain short interfering RNA (siRNA) have been extensively investigated for clinical applications. LNPs are generally prepared by an alcohol dilution method. In this method, it is necessary to remove the alcohol and then concentrate the LNP sample before they can be used. In this study, we report on the development of an "alcohol dilution-lyophilization method" for preparing siRNA-encapsulating LNPs. This method involves the use of a freeze-drying (lyophilization) method to remove the residual alcohol and to simultaneously concentrate the preparation. At first, the compositions of cryoprotectants and polyethylene glycol (PEG)-lipids that were used were optimized from the point of view of particle stabilization. A combination of sucrose and 1-(monomethoxy polyethyleneglycol5000)-2,3-dimyristoylglycerol (DMG-PEG5000) was found to have the most efficient cryoprotective activity for the LNPs. The knockdown efficiency of the LNP prepared by the alcohol dilution-lyophilization method was comparable to that of an LNP prepared by the conventional ultrafiltration method.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Shirane D,Tanaka H,Nakai Y,Yoshioka H,Akita Hdoi
10.1248/bpb.b18-00208subject
Has Abstractpub_date
2018-01-01 00:00:00pages
1291-1294issue
8eissn
0918-6158issn
1347-5215journal_volume
41pub_type
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