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

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-PTX-PA(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。

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

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.