阿克拉霉素A长循环微乳用于肿瘤小剂量化疗

Anticancer effect of aclacinnomycin a long circulation microemulsions in small dosage chemotherapy

目的:制备阿克拉霉素A的长循环微乳(aclacinomycin A long circulation micoremulsions,ALM)用于肿瘤的小剂量化疗。方法:以聚乙二醇-二硬脂酰基磷脂酰乙醇胺为表面活性剂,制备了ALM,并测定了其理化性质。通过比较ALM与阿克拉霉素A(ACA)的血药浓度和急性毒性,评价了ALM的长循环及其降低ACA毒性的作用。采用小剂量化疗方案给药,评价了ALM的抗肿瘤作用。结果:ALM的粒径为(118.4±8.2)nm,Zeta电位为(-32.6±7.2)mV,载药率为(98.2±1.6)%(n=3)。与ACA相比,ALM的血药浓度显著提高,急性毒性较低,抗肿瘤作用较强,且更适用于肿瘤的小剂量化疗(P<0.01)。结论:ALM有可能成为一种适用于肿瘤小剂量化疗的药物。

OBjECTIVE To prepare aclacinomycin A（ACA）long circulation microemulsions （ALM） and evaluate its acute toxicity and anticancer effect in cancer small dosage chemotherapy. METHODS ALM was prepared using polylene glycol derivative of distearoylphosphatidyl ethanolamine（PEG-DSPE） and characterized using its particle size distribution, Zeta potential and loading efficiency. The ACA plasma level and acute toxicity of ALM were compared with those of ACA in mice. FoIlowing small dosage chemotherapy, the anticancer effect of ALM was evaluated in animal tumor models. RFNULIS The average diameter of ALM was （ 118. 4 ± 8. 2） nm while its Zeta potential was （ - 32. 6 ± 7.2） mV and its loading efficiency was （98. 2 ± 1.6）N （N= 3）. ALM showed longer circulation time in blood than ACA significantly while its acute toxicity was lower than that of ACA. Following small dosage chemotherapy, ALM showed greater anticancer effect than ACA while both of them were more effective than its corresponding single dose. CONCLUSION ALM is less toxic than ACA, and may become a better candidate for cancer small dosage chemotherapy.