| Cancer is the most common and serious disease that directly endangers human life in today's world.Now it has become the number one killer to people in this globe.The traditional methods of cancer treatment usually include surgical opration,chemical therapy,radio-therapy,etc.,but all of them are hurting the body.In recent years,nano-drugs have made great progress in the detection,diagnosis and treatment of tumor,which has become one of the hot spots in the research of antitumor agents.As main bioactive constituent in some medicine plant,Kaempferol(3,4',5,7-four hydroxyl flavone)belongs to flavonoids with the activities on antitumor,antioxidant,antibacterial,In this paper,flexible liposomes as materials,preparation for anti-tumor kaempferol-Flexible liposome nanoparticles by emulsion solvent evaporation method,and the effects of kaempferol on flexible liposome nanoparticles morphology,encapsulation efficiency,drug loading in vitro release behavior and pharmacokinetic behavior were investigated.Firstly,a HPLC method was established for determining kaempferol in flexible liposome nanoparticles.The conditions of high performance liquid chromatography as follow: column is Diamonsil-C18(250mm * 4.6mm,5 m);the mobile phase was methanol and 0.4% aqueous solution of phosphoric acid(70:30);the detection wavelength is 361 nm;the flow rate was 1.0m L·min-1;sample size is 10 ?L;column temperature is sea at 30 ?.Analysis of methodological inspection,kaempferol control in 0.1 mg/m L~0.6 mg/m L,the relationship between peak area and concentration showed a linear relationship,the linear regression equation was A=457556C-25310(R2=0.9994).In addition,the experimental results of precision,recovery,stability and specificity of the method meet the requirements of drug testing.Secondly,this paper studies the method of preparation of kaempferol flexible liposome nanoparticles prepared by solvent evaporation.Based on the particle size and particle size distribution(Size)(PDI),encapsulation efficiency as indexes,the effects of the kinds and concentration of surfactant,water volume,lecithin concentration of four factors on the flexible liposome nanoparticles had been researched by single factor single factor test and orthogonal test,and then the optimal preparation conditions was gained.The experimental results show that the optimal conditions was in 5 mg kaempferol solved in 2 m L acetone,20 mg lecithin added to get oil phase;the 2% sodium deoxycholate as surfactant formed the 70 m L aqueous solution.In the stirred state,the organic phase was slowly dripped into the aqueous phase to obtain a mixed solution.After 3 minutes of ultrasonic treatment and acetone distillation,the kaempferol flexible liposome nanoparticles were prepared.Three batches of samples were prepared according to the optimum conditions.The average size of the samples was 217.5 nm and the encapsulation efficiency was 76.36%.On the basis of the above research,this paper also investigated the methods of preparation of lyophilized powder of kaempferol flexible liposome nanoparticles.First,the appearance,color,redispersibility and entrapment efficiency of freeze-dried powder,which were taken as indicators to investigate the dosage of lyophilized protector and lyophilized protective agent.At last,2% lactose was used as lyophilization protectant.At the same time,the quality evaluation of freeze-dried powder was done.The results showed that the appearance of freeze-dried powder was good.The particle size and entrapment efficiency of nanoparticles were not changed before and after freeze-drying.At 4 ?,the leakage rate was 6.21% and the drug loading decreased by 0.61% for 6 months.There was no obvious change in encapsulation efficiency and particle size.Preliminary stability investigation showed that its stability was good and achieved the expected purpose.Finally,the kaempferol flexible liposome lyophilized nanoparticles in vitro release process and its law have been studied.The results show that kaempferol flexible liposome nanoparticles have the behavior of Weibull model of drug for its release is most similar to that of related parameters;pharmacokinetics in rats,nanoparticles group and kaempferol emulsion group have significant differences in the administration of the same dose of cases(P< 0.01),showing significant difference respectively in the following several aspects,such as AUC0-t(of trapezoidal calculated),t1/2,Cmin,DF(T)and CL(clearance)etc.The T1/2 of kaempferol flexible liposome nanoparticles group(elimination half-life)is 1.65 times of the emulsion group,which increases the contact time of tumor lesion cells with drugs,to a certain extent,improve the efficacy of anticancer drugs.To sum up,the prepared by emulsion solvent evaporation method of kaempferol-Flexible liposome nanoparticles morphology was not only rounded appearance with good stability,but also has relatively high encapsulation efficiency,particle size observation results show that its distribution is smaller,and observed that nanoparticles in a certain extent and sustained.Obviously change the pharmacokinetics of kaempferol,slow down the elimination of the drug,and the bioavailability of the drug has been improved.The results of this paper provide scientific basis for the application of kaempferol-flexible liposome nanoparticles in anti-tumor. |
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