紫杉醇棕榈酸酯白蛋白纳米粒的制备及药效和骨髓抑制毒性评价  

Preparation and Pharmacodynamics and Bone Marrow Suppression Toxicity Evaluation of Nab-PTX-PA

作　　者：陈新美 许幼发 林志浙 顾永卫 武鑫 陈建明[1] CHEN Xin-mei;XU You-fa;LIN Zhi-zhe;GU Yong-wei;WU Xin;CHEN Jian-ming(Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Jiaxing Key Laboratory of Oncological Photodynamic Therapy and Targeted Drug Research,Jiaxing 314000,China;Shanghai Weier Laboratory,Shanghai 201712,China)

机构地区：[1]福建中医药大学,福州350122 [2]嘉兴市肿瘤光动力靶向药物研究重点实验室,浙江嘉兴314000 [3]上海维洱实验室,上海201712

出　　处：《中国药学杂志》2022年第7期549-553,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(81772749);福建中医药大学高层次人才科研启动资金项目资助(X2019006-人才);上海青浦区产学研合作发展资金项目资助资助(青产学研2019-5)。

摘　　要：目的制备紫杉醇棕榈酸酯白蛋白纳米粒(Nab-PTX-PA)冻干粉,对其抑瘤效果和骨髓抑制毒性进行评价。方法采用纳米颗粒白蛋白结合技术(Nab^(TM)技术)制备Nab-PTX-PA冻干粉,对Nab-PTX-PA处方的形态、粒径和电位进行表征并比较Nab-PTX-PA冻干前和冻干复溶后粒径、电位的变化。通过构建4T1荷瘤小鼠模型,考察Nab-PTX-PA的抗肿瘤活性。荷瘤小鼠药效给药结束后取血进行血常规检测,考察该制剂的骨髓抑制毒性。结果本研究成功制备了外观平整饱满、生理盐水复溶后再分散性良好的Nab-PTX-PA冻干粉,且制备Nab-PTX-PA冻干粉粒径为(87.63±1.15)nm(n=3),Zeta电位为(-11.7±0.61)mV(n=3),冻干前和复溶后Nab-PTX-PA的粒径、电位均无明显变化。药效学研究结果表明,Nab-PTX-PA(51.16 mg·kg^(-1))的抗肿瘤作用高于Abraxane^(■)(20 mg·kg^(-1)),且具有统计学意义。骨髓抑制毒性结果表明,Nab-PTX-PA(25.58 mg·kg^(-1))对小鼠的骨髓抑制毒性低于等剂量市售药物Abraxane^(■),Nab-PTX-PA(51.16 mg·kg^(-1))对小鼠的骨髓抑制毒性与市售药物Abraxane^(■)(20 mg·kg^(-1))相当。结论采用Nab^(TM)技术制备的Nab-PTX-PA冻干粉性质稳定,Nab-PTXPA(25.58 mg·kg^(-1))与等剂量的Abraxane^(■)(20 mg·kg^(-1))相比,降低了骨髓抑制毒性,Nab-PTX-PA(51.16 mg·kg^(-1))和Abraxane^(■)(20 mg·kg^(-1))毒性相同时,抗肿瘤效果较为明显。OBJECTIVE To prepare a lyophilized powder of paclitaxel palmitate albumin nanoparticles(Nab-PTX-PA)was prepared,and its antitumor effect and bone marrow suppression toxicity were evaluated.METHODS Nanoparticle albumin evaluate(Nab^(TM) technology)was used to prepare Nab-PTX-PA.The morphology,particle size and potential of Nab-PTX-PA formulation were characterized and compared before and after lyophilization of Nab-PTX-PA Changes in particle size and potential after reconstitution.By constructing a 4T1 tumor-bearing mouse model,the anti-tumor activity of Nab-PTX-PA was investigated.After the administration of tumor-bearing mice,routine blood tests were conducted to investigate the bone marrow suppression toxicity of the preparation.RESULTS In this study,Nab-PTX-PA lyophilized powder with smooth and full appearance and good dispersibility after reconstitution in normal saline was prepared,and the particle size of Nab-PTX-PA lyophilized powder was(87.63±1.15)nm(n=3).The Zeta potential was(-11.7±0.61)mV(n=3),and the particle size and potential of Nab-PTX-PA did not change significantly before lyophilization and after reconstitution.The results of pharmacodynamic studies showed that the antitumor effect of Nab-PTX-PA(51.16 mg·kg^(-1))was higher than that of Abraxane^(■)(20 mg·kg^(-1)),and it was statistically significant.Bone marrow suppression toxicity results show that Nab-PTX-PA(25.58 mg·kg^(-1))has lower bone marrow suppression toxicity in mice than the equal-dose commercially available drug Abraxane^(■),while Nab-PTX-PA(51.16 mg·kg^(-1))of bone marrow suppression toxicity is comparable to the commercially available drug Abraxane^(■)(20 mg·kg^(-1)).CONCLUSION Nab-PTX-PA lyophilized powder prepared by Nab^(TM) technology has stable properties.Nab PTX PA(25.58 mg·kg^(-1))and the same dose of Abraxane^(■)(20 mg·kg^(-1)),nab PTX PA(51.16 mg·kg^(-1))and Abraxane^(■)(20 mg·kg^(-1))has the same toxicity,and the antitumor effect is obvious.

关 键 词：紫杉醇棕榈酸酯 前药 白蛋白 药效学 骨髓抑制毒性 

分 类 号：R944[医药卫生—药剂学]