| Celecoxib（CX）-casein（CS）nanoparticles are relatively unstable,and it is easy to precipitate CX during the course of administration to affect their pharmacodynamics.（1）The operation process of preparing CS-CX-NPs by ultrasonic method was determined,and then the stabilization effect of different stabilizers on nanoparticles was studied.Finally,PEG class had a better effect on enhancing the stability of CS-CX-NPs.The stability of PEG35000-CS-CX-NPs modified by PEG35000 increased from less than 10 minutes before modification to 4-6 hours,and the nanoparticles with low CX loading were more stable.When the CX loading was 10 mg/g,the stability of CS-CX-NPs remained unchanged after 6 months of refrigeration.The effect of PEG modification may be from the effect of PC,which close the gap on the surface of nanoparticles,inhibit CX precipitation from nanoparticles,and stabilize the nanosystem.（2）According to the preparation method of PEG35000-CX-CS-NPs,the pepsinase inhibitor（PN）was added to prepare the anti-peptic enzyme degradation PN-PEG35000-CX-CS-NPs agaist pepsinase degradation which is stable at 37℃for about 2.5 h,though the stability of PN-PEG35000-CX-CS-NPs is lower than that of PEG35000-CX-CS-NPs.（3）The transmembrane transport of PEG35000-PN-CX-CS-NPs,PEG35000-CX-CS-NPs and CX-CS-NPs dispersions with different stability was compared and studied.It was found that the stability of nano-CX had a great influence on the absorption of CX due to the difference of transmembrane transport ability.（4）The inhibitory activity of nano-CX on gastric cancer（NCI-N87）was studied in vitro and in vivo.The results showed that the stability of CX nanoparticles had a great influence on the anti-tumor activity of CX.PEG35000-CX-CS-NPs with high stability were beneficial to the absorption and uptake of cells in vivo,thus the anti-tumor effect of CX was significantly improved.The research results of this paper have a certain guiding role for the development of nano-CX products. |
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