紫杉醇PLGA纳米粒注射剂对小鼠肺转移黑色素瘤的治疗作用

摘要

目的 评价紫杉醇聚丙交酯乙交酯纳米粒(PTX-NPs)注射剂对小鼠黑色素瘤肺转移模型的生长抑制效果并探讨其作用机制.方法 采用改良的乳化分散法制备PTX-NPs.建立小鼠黑色素瘤肺转移模型,并将60只荷瘤鼠随机分成4组,PTX-NPs组、PTX组、对照组(给予0.9％氯化钠溶液)及空白载体材料组,每组各15只.每3d尾静脉注射给药5 mg· kg-1,共5次.小鼠于接种细胞30 d后处死,观察肺部情况并用免疫组化方法评价肿瘤组织的增殖及侵袭能力.以高效液相色谱(HPLC)法检测小鼠血浆及心、肝、脾、肺、肾组织中的药物浓度.结果 制备的TAX-NPs包封率达65％,粒径分布为80～100 nm.PTX-NPs对黑色素瘤肺转移模型具有良好的抑制作用,免疫组化检测PTX-NPs组PCNA阳性细胞数为(125±16),HIF阳性细胞数为(27±10),与PTX组[分别为(217±19)及(94±15)]比较差异有统计学意义(P＜0.01).HPLC结果显示末次给药后24 h PTX-NPs组肺组织的药物含量为(5.73±0.25)μg· g-1,明显高于TPTX组(0.66±0.02)μg·g-1(P＜0.01).结论 PTX-NPs注射剂可显著抑制小鼠黑色素瘤肺转移模型的生长及转移,并具有一定的肺部靶向性.%Objective To investigate the inhibition effect of paclitaxel polylactide glycolide nanopartioles (PTX-NPs) injection on mouse lung metastatic melanoma model and its mechanism. Methods The PTX-NPs were prepared by an improved emulsifieation-diffusion method and the murine lung; metastatic melanoma model were established. A total of 60 tumor-bearing mice then were divided into four groups (n= 15) , PTX-NPs, commercially available paclitaxel (PTX) group, control (saline) group and vehicle (Blank-NPs) group. The antitumor effect of paclitaxel nanoparticles in vivo has been evaluated by observing lung condition, and assessing tumor tissue proliferation and invasion with immunohistochemistry 30 d after tumor inoculation. The mice were i. v. injected every 3 d, for total 5 times. Drug concentrations in mouse plasma, heart, liver, spleen, lung and kidney were determined by high-performance liquid ehromatography ( HPLC). Results The entrapment efficiency of PTX-NPs was 65% , and the particle size distribution was 80-100 nm. FPX-NPs showed good suppression against lung metastatic melanoma model. The number of PCNA-positive cells( 125±16) and HIF-positive cells(27±10) detected by immunohistochemistry in the PFX-NPs group exhibited significant difference compared with those in the PTX group [(217±19)and (94±15) ] (P<0. 01 ).The HPLC results showed that the drug content in the lung of PTX-NPs group was (5.73±0.25) μg·g-1 24 h after the last administration, which was significantly higher than that of the PTX group (0.66±0.02)μg·g-1(P<0.01). Conclusion PTX-NPs injection significantly inhibits the growth and metastasis of B16 carcinoma and exerts lung targeted effects.