Curative Effect Of Polyphyllin Hydrogel On Malignant Tumor

Background:Polyphyllin I(PPI)has been proved to have good antitumor effect on many tumor cell lines in vitro.However,it has poor solubility,controversial safety and the anti-tumor effect is not supported by in vivo experimental results.Methods:1.The H22 subcutaneous tumor model was established and these Kunming mice should be divided into 5 groups:(1)PPI intraperitoneal injection of high dose group(IP-H,30mg/kg),(2)PPI intraperitoneal injection of middle dose group(IP-M,20mg/kg),(3)PPI intraperitoneal injection of low dose group(IP-L,10mg/kg),(4)PPI intratumoral injection of low dose group(IT-L,10mg/kg),(5)saline(control).We injected each group once and killed mice on day 12 to investigate the anti-tumor effect,effective concentration and safety of PPI in vivo.2.Models of H22 subcutaneous tumor were established to observe the distribution and degradation of PPI hydrogel in vivo.The mice were divided into 5 groups to verify the anti-tumor effect.They were:intraperitoneal injection of Paris saponin solution(20mg/kg),intratumoral injection of Paris saponin solution(10mg/kg),paratonin saponins hydrogel injection(10mg/kg),blank hydrogel tumor group injection group and blank control group.The anti-tumor effect of PPI hydrogel could be verified and the mechanisms can be explored by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL),proliferating cell nuclear antigen(PCNA)and anti-angiogenesis test.3.Ascites models were established to observe ascites formation and long-term survival of mice.Results:In subcutaneous tumor model,PPI could significantly inhibit tumor growth by intraperitoneal(IP)injection.The anti-tumor effect increased with the increase of drug concentration,but was not significantly enhanced when the drug concentration was more than 20mg/kg.The efficacy of low dose intratumoral(IT)injection is similar to that of medium and high dose intraperitoneal injection.Hydrogel system can prolong drug release,and the Polyphyllin I gel group(PPI-gel group)has better anti-tumor effect than the Intratumoral injection group(IT group).In the ascites model,the hydrogel of PPI can inhibit the formation of ascites.The hepatotoxicity and nephrotoxicity of different models and treatment methods were not obvious.Conclusion:PPI shows favorable anti-tumor effect and safety on subcutaneous tumor.The hydrogel delivery system achieve a superior anti-tumor effect with slow drug release rate.