Journal
ANALYTICAL BIOCHEMISTRY
Volume 421, Issue 2, Pages 477-481Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ab.2011.09.024
Keywords
Controlled release; Organophosphorus acid anhydrolase; Mesoporous silica; Organophosphorus nerve agents
Funding
- National Institutes of Health (NIH)
- National Institute of General Medical Sciences [R01GM080987]
- office of Basic Energy Sciences of the U.S. Department of Energy [KC020105-FWP12152]
- Transformational Materials Science Initiative of the Pacific Northwest National Laboratory (PNNL)
- Battelle [DE-AC06-RLO1830]
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We report here that under different physiological conditions, biomolecular drugs can be stockpiled in a nanoporous support and afterward can be instantly released when needed for acute responses, and the biomolecular drug molecules can also be gradually released from the nanoporous support over a long time for a complete recovery. Organophosphorus acid anhydrolase (OPAA) was spontaneously and largely entrapped in functionalized mesoporous silica (FMS) due to the dominant electrostatic interaction. The OPAA-FMS composite exhibited a burst release in a pH 9.0 NaHCO3-Na2CO3 buffer system and a gradual release in pH 7.4 simulated body fluid. The binding of OPAA to NH2-FMS can result in less tyrosinyl and tryptophanyl exposure OPAA molecules to aqueous environment. The bound OPAA in FMS displayed lower activity than the free OPAA in solution prior to the enzyme entrapment. However, the released enzyme maintained the native conformational structure and the same high enzymatic activity as that prior to the enzyme entrapment. The in vitro results in the rabbit serum demonstrate that both OPAA-FMS and the released OPAA may be used as a medical countermeasure against the organophosphorus nerve agents. (C) 2011 Elsevier Inc. All rights reserved.
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