阿霉素及卡铂双载药脂质体治疗卵巢癌腹水的研究  

Study on doxorubicin and carboplatin co-loaded liposome in the treatment of ovarian cancer ascites

作　　者：孙瑶 刘红婷 刘曚晗 罗之林 艾笑羽 杨诚[1] SUN Yao;LIU Hongting;LIU Menghan;LUO Zhilin;AI Xiaoyu;YANG Cheng(College of Pharmacy,Nankai University,Tianjin 300350,China)

机构地区：[1]南开大学药学院,天津300350

出　　处：《沈阳药科大学学报》2024年第5期537-543,674,共8页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(81803458)。

摘　　要：目的研究阿霉素及卡铂双载药脂质体对卵巢癌腹水的治疗。方法采用薄膜分散法结合硫酸铵梯度法制备阿霉素-卡铂脂质体(doxorubicin-carboplatin liposome,DOX/CBP-Lip),考察其粒径、电位、包封率、载药量和体外药物释放性能,对其体外抗肿瘤活性进行初步研究,评价其体内药效,包括腹围、体质量变化和生存率情况。结果DOX/CBP-Lip的粒径为177.90 nm,电位为-32.63 mV,其中CBP的包封率在49.04%左右,DOX的包封率在93.17%左右,且有一定的缓释作用。DOX/CBP-Lip对OVCAR3细胞具有协同抗肿瘤的作用,在相同给药剂量下,DOX/CBP-Lip可以发挥协同作用,增强药物的抗肿瘤活性,降低药物毒性。结论将DOX和CBP制成双载药脂质体可以提高卵巢癌引发腹水的治疗效果,降低DOX和CBP的毒性,为联合使用抗肿瘤药物治疗肿瘤引起的腹水提供参考。Objective To study the treatment of ovarian cancer ascites with doxorubicin and carboplatin co-loaded liposomes.Methods The doxorubicin(DOX)and carboplatin(CBP)co-loaded liposomes(DOX/CBP-Lip)were prepared by thin film dispersion method combined with ammonium sulfate gradient method.Then the liposomes were characterized by particle size,Zeta potential,encapsulation efficiency,drug loading and in vitro drug release.In addition,the efficacy of the co-loaded liposomes in vivo was further evaluated.The body weight,abdominal circumference and survival rate were used as indicators.Results The particle size of DOX/CBP-Lip was 177.90 nm,and the Zeta potential was-32.63 mV.Moreover,the encapsulation efficiency(EE)of CBP was about 49.04%,and the drug loading(DL)of DOX was about 2.52%.More importantly,the in vitro drug release results indicated that DOX/CBP-Lip had the certain sustained release effect.At the same dose,DOX/CBP-Lip showed a synergistic antitumor effect on OVCAR3 cells,and played a synergistic role in enhancing the antitumor activity of drugs and reducing drug toxicity.Conclusion The combined administration of DOX and CBP could improve the symptoms of ascites caused by ovarian cancer and reduce the toxicity of DOX and CBP.The dosage form provides a reference for the combined use of anti-tumor drugs in the treatment of ascites caused by tumors.

关 键 词：阿霉素 卡铂 脂质体 联合给药 卵巢癌腹水 

分 类 号：R94[医药卫生—药剂学]