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 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.
Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Baowei
B
Chen
Saumil S
SS
Shah
Yongsoon
Y
Shin
Chenghong
C
Lei
Jun
J
Liu
D000818:Animals; D043303:Aryldialkylphosphatase / Q000737:chemistry*; D002619:Chemical Warfare Agents / Q000737:chemistry* / Q000633:toxicity; D004800:Enzymes, Immobilized / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D009420:Nervous System / Q000187:drug effects*; D011817:Rabbits; D012822:Silicon Dioxide / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
D002619:Chemical Warfare Agents; D004800:Enzymes, Immobilized; D012822:Silicon Dioxide; D043303:Aryldialkylphosphatase