Preparation Of Casein-celecoxib Nanoparticles And Their Antitumor Effect

In recent years,many studies have shown that celecoxib-a non-steroidal anti-inflammatory drug(NSAIDs)-has many therapeutic effects on tumor prevention and treatment,and its anticancer mechanism is mainly due to the inhibition on cell proliferation and apoptosis.Nevertheless,only oral preparation of celecoxib was used in clinic.After the drug administration,celecoxib is prone to accumulate in the gastrointestinal tract,which leads to a high drug concentration in the local area and series of adverse reactions within the gastrointestinal tract.This usually results in the low bioaccessibility and bioavailability of celecoxib.In this paper,casein,as a natural and non-toxic carrier polymer,was used to develope a novel nano-injection formula.Our results showed that the entrapment efficiency and stability of celecoxib nanoparticles were significantly improved by using the new formula.Moreover,a sustained-release behavior was observed according to the pharmacokinetic studies.Consequently,the occurrence of some gastrointestinal adverse reactions can be reduced.It may provide a theoretical basis for the practical application of celecoxib and casein.The main research results of this thesis are listed as follows:(1)The prepared casein celecoxib nanoparticles had good stability and embedding rate.The best preparation formula contained 100 mg/ml celecoxib solution(25 ?L),compound A solution(25 ?L),and compound B solution(25 ?L).The particle size and absolute potential of nanoparticle formed in this way were 154.2 nm(PDI = 0.270)and 43.05 mV,respectively.In addition,the drug loading reached 0.41 mg/ml,with an embedding rate of 81.3%.The system was stable for 3 h at 37 ° C.(2)Through the in vitro test on tumor cells,casein-celecoxib nanoparticles had an inhibiting effect on the cell viability of melanoma(A375)cells and non-small cell lung cancer(A549)cells.The morphology of A375 and A549 cells was also affected by the celecoxib-loaded nanoparticles.In particular,when the concentration of celecoxib in casein-celecoxib nanoparticles reached 15 ?g/ml,the inhibitory activity against A375 tumor cells was maximized(90%).In parallel,when the concentration of celecoxib reached 30 ?g/ mL,the viability of A549 tumor cells was inhibited by 90%.On contrary,the blank carrier – stabilizer A and stabilizer B in the nanoparticles–had no inhibitory effect on A375 and A549 cells.Moreover,casein-celecoxib nanoparticles affected the cell morphology of A375 and A549,and promoted cell apoptosis by destroying the structure of the cells and reducing the life activity of the cells.It was further verified that casein-celecoxib nanoparticles could play an anti-tumor role to some extent.(3)In the animal experiments,each mouse was injected into caudal vein every 72 hours with a daily dose of 7 mg/kg or 14 mg/kg for 24 days.The in vivo studies showed that caseincelecoxib nanoparticles(drug dosage = 7 mg/kg)inhibited tumors by 46%;when the drug concentration was raised to 14 mg/kg,the tumors were depressed by 51%.That is,high doses of celecoxib nanoparticles showed slightly higher tumor inhibition rate.However,no dose-dependent effect of celecoxib nanoparticles was observed on A375 tumor cells.At the end of the experiment,there was no significant change in body weight of the casein-celecoxib nanoparticle group,further indicating that the casein-celecoxib nanoparticles were not significantly toxic to the test mice in vivo.