Title
Identification of Excipients for Stabilizing Fiberless Adenovirus as Biopharmaceuticals
Author
Grit Kupgan, Shyamal P. Choudhari, Nicholas H. Flynn, Adane Nigatu, Sravanthi Vupputuri, William D. Picking, Wendy L. Picking, Joshua D. Ramsey
Year
2017
Journal
Journal of Pharmaceutical Sciences
Abstract
Reducing the promiscuous tropism of native adenovirus by using fiberless adenovirus is advantageous towards its use as a gene therapy vector or vaccine component. The removal of the fiber protein on native adenovirus abrogates several undesirable interactions; however, this approach decreases the particle’s physical stability. In order to create stable fiberless adenovirus for pharmaceutical use, the effects of temperature and pH on the particle’s stability profile must be addressed. Our results indicate that the stability of fiberless adenovirus is increased when it is stored in mildly acidic conditions around pH 6. The stability of fiberless adenovirus can be further enhanced by employing excipients. Excipient screening results indicate that the non-ionic surfactant Pluronic F-68 and the amino acid glycine are potential stabilizers because of their ability to increase the thermal transition temperature of the virus particle and promote retention of biological activity after exposure to prolonged thermal stress. Our data indicate that the instability of fiberless adenovirus can be ameliorated by storing the virus in the appropriate environment and it should be possible to further optimize the virus so that it can be used as a biopharmaceutical.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Chemical stability, Thermal stability, Thermodynamics, Biochemistry, Pharmaceutical