二氧化锰包覆的聚乳酸羟基乙酸共聚物载血卟啉单甲醚纳米粒的药动学检测和抑瘤效果
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摘要
目的:考察二氧化锰包覆的聚乳酸羟基乙酸共聚物载血卟啉单甲醚(HMME)纳米粒(PLGA/HMME@MnO2)的药动学和对肿瘤的抑制作用。方法:对SD大鼠尾静脉注射HMME、PLGA/HMME和PLGA/HMME@MnO2,采用高效液相色谱法考察3种制剂在大鼠体内的药动学特征。S180荷瘤小鼠肿瘤模型建立后,动物分组如下:生理盐水组、生理盐水+激光组、HMME+激光组、PLGA/HMME+激光组、PLGA@MnO2、PLGA/HMME@MnO2+激光组,其中HMME给药剂量为3.0 mg/kg,尾静脉注射给药,2 d给药一次,共5次。给药4 h后在肿瘤部位施加532 nm激光(1.5 W/cm2,1.5 min)照射。记录分析相对肿瘤体积变化和体重变化。结果:与HMME相比,PLGA/HMME和PLGA/HMME@MnO2均延长了药物在血液中的循环时间,半衰期分别为HMME的2.71和9.32倍。治疗结束时,PLGA/HMME@MnO2+激光组相对肿瘤体积最小(1.49±0.44)。结论:PLGA/HMME@MnO2延长了HMME的血液循环时间,并提高了其光动力抗肿瘤效果。
Aim:To investigate the pharmacokinetics and antitumor effect of manganese dioxide-coated HMME-loaded polylactide-co-glycolide nanoparticles.Methods:The rats were injected with HMME,PLGA/HMME and PLGA/HMME@MnO2 via tail vein,respectively.The pharmacokinetics study of the three different formulations was performed by HPLC.The S180 tumor-bearing mice were allocated into the following six groups.The mice were treated with normal saline,normal saline + 532 nm laser,HMME + 532 nm laser,PLGA/HMME + 532 nm laser,PLGA@ MnO2,and PLGA/HMME@ MnO2+532 nm laser,respectively.The dosage of HMME was 3.0 mg/kg.These various formulations were injected every 2 days for 5 times via tail vein.For the groups with irradiation,532 nm laser at a power density of 1.5 W/cm2 was carried out for1.5 min on the tumor site after injection.The antitumor effect was investigated according to the relative tumor volume.Besides,the mice weight was also monitored for evaluating the toxicity of the system.Results:PLGA/HMME and PLGA/HMME@ MnO2 possessed prolonged circulation property compared with HMME.And the half life time of PLGA/HMME and PLGA/HMME@ MnO2 was 2.71 and 9.32 times as compared with that of free HMME,respectively.At the end of the therapeutic period,the relative tumor volume of the mice from PLGA/HMME@ Mn O2+ 532 nm laser group was the smallest(1.49±0.44),showing difference compared with other groups.Conclusion:Manganese dioxide-coated HMME-loaded polylactide-co-glycolide nanoparticles increase the circulation time of HMME,and improves the antitumor efficiency.
Aim:To investigate the pharmacokinetics and antitumor effect of manganese dioxide-coated HMME-loaded polylactide-co-glycolide nanoparticles.Methods:The rats were injected with HMME,PLGA/HMME and PLGA/HMME@MnO2 via tail vein,respectively.The pharmacokinetics study of the three different formulations was performed by HPLC.The S180 tumor-bearing mice were allocated into the following six groups.The mice were treated with normal saline,normal saline + 532 nm laser,HMME + 532 nm laser,PLGA/HMME + 532 nm laser,PLGA@ MnO2,and PLGA/HMME@ MnO2+532 nm laser,respectively.The dosage of HMME was 3.0 mg/kg.These various formulations were injected every 2 days for 5 times via tail vein.For the groups with irradiation,532 nm laser at a power density of 1.5 W/cm2 was carried out for1.5 min on the tumor site after injection.The antitumor effect was investigated according to the relative tumor volume.Besides,the mice weight was also monitored for evaluating the toxicity of the system.Results:PLGA/HMME and PLGA/HMME@ MnO2 possessed prolonged circulation property compared with HMME.And the half life time of PLGA/HMME and PLGA/HMME@ MnO2 was 2.71 and 9.32 times as compared with that of free HMME,respectively.At the end of the therapeutic period,the relative tumor volume of the mice from PLGA/HMME@ Mn O2+ 532 nm laser group was the smallest(1.49±0.44),showing difference compared with other groups.Conclusion:Manganese dioxide-coated HMME-loaded polylactide-co-glycolide nanoparticles increase the circulation time of HMME,and improves the antitumor efficiency.
引文
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[2]李若虹.血卟啉单甲醚光动力治疗鲜红斑痣的临床和基础研究[D].北京:中国医学科学院北京协和医学院中国医学科学院清华大学医学部,2011.
[3]许德余,陈文晖,张浩,等.光动力治癌新药血卟啉单甲醚(HMME)的研究[J].中国激光医学杂志,1993,2(1):3
[4]SHI J,YU X,WANG L,et al.PEGylated fullerene/Iron oxide nanocomposites for photodynamic therapy,targeted drug delivery and Mr imaging[J].Biomaterials,2013,34(37):9666
[5]李洁,佘振南,邓意辉.高渗透长滞留效应理论在肿瘤靶向药物传递系统设计中的应用进展[J].沈阳药科大学学报,2013,30(2):150
[6]LUK BT,ZHANG LF.Current advances in polymer-based nanotheranostics for cancer treatment and diagnosis[J].ACS Appl Mater Interfaces,2014,6(24):21859
[7]BOIX-GARRIGA E,ACEDO P,CASADO A,et al.Poly(D,L-lactide-co-glycolide)nanoparticles as delivery agents for photodynamic therapy:enhancing singlet oxygen release and photototoxicity by surface PEG coating[J].Nanotechnology,2015,26(36):365104
[8]SHI JL,SUN BL,SHI W,et al.Decreasing GSH and increasing ROS in chemosensitivity gliomas with IDH1 mutation[J].Tumor Biol,2015,36(2):655
[9]FAN HH,YAN GB,ZHAO ZL,et al.A smart photosensitizer-Manganese dioxide nanosystem for enhanced photodynamic therapy by reducing glutathione levels in cancer cells[J].Angew Chem Int Ed Engl,2016,55(18):5477
[10]GORDIJO CR,ABBASI AZ,AMINI MA,et al.Design of hybrid MnO2-polymer-lipid nanoparticles with tunable oxygen generation rates and tumor accumulation for cancer treatment[J].Adv Funct Mater,2015,25(12):1858