Robert E. Sievers
Analytical, Pharmaceutical and
Ph.D. University of Illinois, 1960
Director, Environmental Program
Professor, Chemistry and Biochemistry
Professor Sievers is studying analytical chemistry, pharmaceutical science, aerosols, microparticles and nanoparticles, inhalable vaccines and antibiotics, and supercritical fluids.
Fundamental and applied studies of the formation of nanoparticle and microparticle aerosols are underway. Carbon dioxide-assisted nebulization provides superior aerosols for various forms of spectroscopy, such as electro-spray ionization, mass spectrometry and atomic absorption. Sievers' students are collaborating with pharmacists and physicians in the University of Colorado Health Sciences Center of Pharmaceutical Biotechnology, to develop new methods for delivery of aerosol particles useful in direct and painless administration of therapeutic drugs and vaccines by inhalation. The drugs are dissolved or suspended in supercritical fluids, and unusually small aerosol particles are formed by rapid decompression to facilitate delivery of the aerosol particles to the most distal alveoli and to allow rapid uptake by the lungs. Formation of fine aerosols is expected to become increasingly important in the treatment or vaccination against measles, HPV, influenza, infections, cystic fibrosis, and asthma.
The simultaneous stabilization, drying, and micronization of vaccines, antibodies, proteins, antibiotics, and anti-inflammatory pharmaceuticals and other products of the biotechnology revolution are under study. Two of the fourteen "Grand Challenges identified by the Bill and Melinda Gates Foundation and the NIH Foundation as critical to world health are being addressed by the Sievers group: needle-free administration of vaccines (by pulmonary or nasal aerosols), and vaccines that do not need refrigeration for long term storage. Collaborations with groups in India and South Africa have been developed.
Current Research: Aerosol Vaccines
The Global Health Group of CIRES is led by myself and Stephen Cape, with the participation of CIRES graduate students David McAdams and J’aime Manion and undergraduate student Nisha Shah. We made continued progress in the development of needle-free delivery systems for vaccines and pharmaceuticals that take advantage of microparticles for inhalation immunization, or, following compression into small pellet lozenges, can be administered sublingually (under the tongue). Sievers has served as principal investigator for five years, leading a team from Aktiv-Dry LLC, the Serum Institute of India, Sristek (in India), the U.S. Centers for Disease Control and Prevention, the Johns Hopkins University, CU-Boulder (headed by Stephen Cape), the University of Kansas, BD Technologies, and the National Jewish Medical and Research Center.
1) Our team has reformulated the injectable Edmonston- Zagreb live attenuated measles virus vaccine, replacing sorbitol with myo-inositol to create an inhalable aerosol measles vaccine. Our patented CAN-BD® process was used to produce micronized measles vaccine dry powder with residual moisture levels of 0.3-1.3 percent. The dry powder vaccine is stable for at least two years at 2-8°C and shows less than 1 log loss of virus infectivity at 37°C for seven days.
2) Our team has learned that inhaled myo-inositol powders and the new dry powder aerosol vaccine are not toxic in two animal models. Our team also determined that, 14 months after groups of Rhesus macaques were immunized by at-liberty inhalation of the new vaccine aerosols through facemasks, they were fully protected from infection when challenged with wild-type measles virus. 3) The team has developed two simple, low-cost, active dry powder inhalers.
4) Plans have been made to start Phase I human clinical trials in the summer of 2010 after Indian regulatory approval is received. Presently, several hundred children die each day in India from measles-related disease. Ten percent of all preschool deaths in Indian children are still caused directly and indirectly by measles. In the improved vaccine developed at CU-Boulder, the dry aerosolized and inhaled microparticles rapidly dissolve in the aqueous film in respiratory tracts, so no purified water for injection is needed. The dry powders are individually sealed in peelable blister packs or rupturable capsules to avoid bacterial contamination sometimes encountered when using multi-dose vials.
Work has also begun to synthesize and compress microparticles into wafers for oral and sublingual delivery. Aerosols of kanamycin and other tuberculosis antibiotics were also synthesized and characterized in 2009.
Honors and Awards
- Tswett Chromatography Medallist, 1981
- American Chemical Society Colorado Section Award, 1985
- Dimick Award in Chromatography, 1992
- Thomas Jefferson Award, 2001
- Robert Stearns Award, 2003
- Pinnacle of Inventorship Award, 2004
- ACS Astellas Prize in Public Health, 2008
- Governor's Award for Research Impact, 2009
Dr. Sievers is a professor at the University of Colorado Boulder.