Construction of Triptolide Prodrug Liposome Nanosystem and Evaluation of Its Anti-Pancreatic Cancer Ac-tivity
OBJECTIVE To prepare triptolide lignoceric acid ester liposome and characterize it,investigate its therapeutic effect on pancreatic cancer.METHODS Firstly,triptolide lignoceric acid ester liposome was prepared by thin film dispersion method,the single factor test and Box-Behnken response surface method were used to optimize the formulation process.Secondly,liposome form was observed using transmission electron microscope,the particle size,the polydispersity index and Zeta potential of the liposome was observed using Malvin particle size instrument and the initial stability of the TPL-LA-lip was investigated.Finally,the anti-pancre-atic activity of TPL-LA-lip in vivo was evaluated by Pane 02 tumor bearing mouse model.RESULTS Triptolide lignoceric acid ester liposome was prepared successfully,and the optimal process and prescription were determined.The liposome was prepared by thin film water method,phospholipid was selected PC-98T,the ratio of drug to phospholipid was 1:10,cholesterol to phospholipid ratio was 1:10,DSPE-mPEG2000 was 0.05％,and the preparation temperature was 55 ℃.The liposome was spherical in appearance,the encap-sulation rate(EE％)was(98.30±0.32)％,the loading efficiency rate(LE％)was(8.33±0.24)％,the particle size was(105.60±0.01)nm,the Zeta potential was(-34.54±0.17)mV,and had good stability.In PBS medium containing 30％etha-nol,the cumulative release of prodrug liposome was 40.35％at 24 h,and it showed good sustained-release effect.At the end of the pharmacokinetics experiment on day 15,the tumor bodies of mice in control,blank lip,TP solution,minnelide and TPL-LA-lip were(849.45±53.72)(880.45±121.45)(602.09±56.80)(265.67±23.12)(237.67±38.30)mm3,respectively.The change rates of body weight were 18.12％,21.29％,-3.62％,13.06％and 19.97％,respectively.Compared with the control and TP groups,the TPL-LA-lip group tumor volume was significantly different(P＜0.05).In addition,there was no significant difference in body weight between the TPL-LA lip group and the negative control group,while the body weight and organs indexs of the mice treated with TP solution were significantly reduced,indicating the good biological safety of TPL-LA-lip.CONCLUSION The high lipophilic trip-tolide lignoceric acid ester prodrug greatly improved the formulation druggability of TP,and the liposome produced had high encapsula-tion rate and good stability.Prodrug technology combined with liposome carrier delivery of TP can significantly enhance the anti-pancre-atic cancer effect of the drug,while reducing toxicity,providing a new idea and experimental basis for the development of triptolide pro-drug nano drug delivery system.
triptolideliposomeBox-Behnken response surface methodologypancreatic cancer
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