In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents.
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 NaHCO(3)-Na(2)CO(3) buffer system and a gradual release in pH 7.4 simulated body fluid. The binding of OPAA to NH(2)-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.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 1036421
- Report Number(s):
- PNNL-SA-73487; ANBCA2; KC0201050; 400412000; TRN: US201206%%294
- Journal Information:
- Analytical Biochemistry, 421(2):477-81, Vol. 421, Issue 2; ISSN 0003-2697
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
60 APPLIED LIFE SCIENCES
BODY FLUIDS
BUFFERS
ELECTROSTATICS
ENZYMES
IN VITRO
NERVES
RABBITS
SILICA
Controlled release
Organophosphorus acid anhydrolase
Mesoporous silica
Organophosphorus nerve agents
CATALYTIC ACTIVITY
ENZYME
CETYLCHOLINESTERASE
DECONTAMINATION
CONFINEMENT
SUPPORTS