~(99)Tc~m-MIBI脂质体纳米粒制备及生物分布实验研究
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摘要
目的探索~(99)Tc~m-MIBI脂质体纳米粒的制备方法,考察其在体外条件下的物理、生物学表征和稳定性,并研究其在小鼠体内的生物学分布特征。方法采用乙醇滴注-超声分散工艺制备~(99)Tc~m-MIBI脂质体纳米粒。测定其粒径及包封率指标。在体外37℃条件下,观察~(99)Tc~m-MIBI脂质体纳米粒在正常人血清和生理盐水中(NS)不同时间点的放化纯及其稳定性,研究其在小鼠体内15、60、120 min的分布特征。结果乙醇滴注-超声分散方法制备的~(99)Tc~m-MIBI脂质体纳米粒在电镜下观察呈球形、均匀,平均粒径(168.2±18.6)nm。体外稳定性实验表明,在正常人血清和NS中将~(99)Tc~m-MIBI脂质体纳米粒孵育15、30、60、120 min,其放化纯分别达96%、93%、90%、89%和92%、89%、86%、85%。体内生物分布实验表明,与~(99)Tc~m-MIBI比较,静脉注射~(99)Tc~m-MIBI脂质体纳米粒后,在观察时间内发现脾脏摄取显著,肾脏的放射性摄取率较低。结论~(99)Tc~m-MIBI脂质体纳米粒的制备方法简单,具有较为理想的物理、生物学表征,在血清中的稳定性较好。与~(99)Tc~m-MIBI比较肾脏摄取率低,在动物体内的循环时间延长。
Objective To explore the method of preparing ~(99)Tc~m-MIBIliposome nanoparticles,investigate its' physical,biological characterization and stability in vitro,and study its biological distribution characteristics in mice. Methods The ~(99)Tc~m-MIBIliposome nanoparticles were prepared by the ethanol infusion-ultrasonic dispersion process. The particle size and encapsulation efficiency were measured. The radioactivity purity and stability of ~(99)Tc~m-MIBIliposome nanoparticles in normal human serum and normal saline( NS) at different time points were observed under the condition of 37 ℃ in vitro. The distribution characteristics of 15,60,and 120 min in mice were studied. Results The ~(99)Tc~m-MIBIliposome nanoparticles prepared by ethanol infusion-ultrasonic dispersion method were spherical and homogeneous under the electron microscope,with an average diameter of( 168. 2 ± 18. 6) nm. In vitro stability test showed that ~(99)Tc~m-MIBIliposome nanoparticles incubated 15,30,60,120 min in normal serum and NS respectively,and their radiochemical purity was96%,93%,90%,89% and 92%,89%,86% and 85%,respectively. In vivo biodistribution experiment showed that compared with ~(99)Tc~m-MIBI,after intravenous injection of ~(99)Tc~m-MIBIliposome nanoparticles,the spleen uptake was significantly observed and the radioactivity uptake rate of kidney was low during the observation time. Conclusion The preparation method of ~(99)Tc~m-MIBIliposome nanoparticles is simple and has ideal physical,biological characterization,and the stability in serum is good. Compared with ~(99)Tc~m-MIBIthe kidney uptake rate was low,and the circulation time in vivo of the mice was prolonged.
Objective To explore the method of preparing ~(99)Tc~m-MIBIliposome nanoparticles,investigate its' physical,biological characterization and stability in vitro,and study its biological distribution characteristics in mice. Methods The ~(99)Tc~m-MIBIliposome nanoparticles were prepared by the ethanol infusion-ultrasonic dispersion process. The particle size and encapsulation efficiency were measured. The radioactivity purity and stability of ~(99)Tc~m-MIBIliposome nanoparticles in normal human serum and normal saline( NS) at different time points were observed under the condition of 37 ℃ in vitro. The distribution characteristics of 15,60,and 120 min in mice were studied. Results The ~(99)Tc~m-MIBIliposome nanoparticles prepared by ethanol infusion-ultrasonic dispersion method were spherical and homogeneous under the electron microscope,with an average diameter of( 168. 2 ± 18. 6) nm. In vitro stability test showed that ~(99)Tc~m-MIBIliposome nanoparticles incubated 15,30,60,120 min in normal serum and NS respectively,and their radiochemical purity was96%,93%,90%,89% and 92%,89%,86% and 85%,respectively. In vivo biodistribution experiment showed that compared with ~(99)Tc~m-MIBI,after intravenous injection of ~(99)Tc~m-MIBIliposome nanoparticles,the spleen uptake was significantly observed and the radioactivity uptake rate of kidney was low during the observation time. Conclusion The preparation method of ~(99)Tc~m-MIBIliposome nanoparticles is simple and has ideal physical,biological characterization,and the stability in serum is good. Compared with ~(99)Tc~m-MIBIthe kidney uptake rate was low,and the circulation time in vivo of the mice was prolonged.
引文
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[14]Han Z,Lv L,Ma Y,et al.Cypate-mediated thermosensitive nanoliposome for tumor imaging and photothermal triggered drug release[J].JBiophotonics,2017,10(12):1607-1616.
[15]Yuan J,Zhou X,Cao W,et al.Improved Antitumor Efficacy and Pharmacokinetics of Bufalin via PEGylated Liposomes[J].Nanoscale Res Lett,2017,12(1):585.
[16]Rangsimawong W,Opanasopit P,Rojanarata T,et al.Skin Transport of Hydrophilic Compound-Loaded PEGylated Lipid Nanocarriers:Comparative Study of Liposomes,Niosomes,and Solid Lipid Nanoparticles[J].Biol Pharm Bull,2016,39(8):1254-1262.
[17]Chen Y,Chen J,Cheng Y,et al.A lyophilized sterically stabilized liposome-containing docetaxel:in vitro and in vivo evaluation[J].JLiposome Res,2017,27(1):64-73.
[18]Mo L,Song JG,Lee H,et al.PEGylated hyaluronic acid-coated liposome for enhanced in vivoefficacy of sorafenib via active tumor cell targeting and prolongedsystemic exposure[J].Nanomedicine,2017,14(2):557-567.
[19]刘凤英,于英杰,郑增娟.药物聚乙二醇化的研究进展[J].海峡药学,2016,28(7):1-4.
[20]Wang JP,Zhou XL,Yan JP,et al.Nanobubbles as ultrasound contrast agent for facilitating small cell lung cancer imaging[J].Oncotarget,2017,8(44):78153-78162.
[2]申勇,孙伟莉,袁超,等.99mTc-MIBI评价2-脱氧-D-葡萄糖对鼻咽癌耐药株多药耐药的逆转作用及机制[J].中国药理学通报,2015,31(10):1433-1438.
[3]Gharehdaghi M,Dabbagh Kakhki VR,Khooei A,et al.Is(99m)TcMIBI scintigraphy a predictor of response to pre-operative neoadjuvant chemotherapy in osteosarcoma?[J].Asia Ocean J Nucl Med Biol,2013,1(2):22-27.
[4]Shi J,Su Y,Liu W,et al.A nanoliposome-based photoactivable drug delivery system for enhanced cancer therapy and overcoming treatment resistance[J].Int J Nanomedicine,2017,2017(12):8257-8275.
[5]Huang FY,Lee TW,Chang CH,et al.Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model[J].Int J Nanomedicine,2015,10(1):463-473.
[6]高惠静,陈蓓,张海波,等.阿苯达唑纳米脂质体冻干粉在大鼠体内药动学及肝靶向研究[J].中国医院药学杂志,2017,37(8):702-706.
[7]李可欣,常莎莎,邸东华,等.配体介导的纳米脂质体作为肿瘤疫苗载体的可行性评价[J].沈阳药科大学学报,2017,34(1):23-27.
[8]Wang X,Liu X,Li Y,et al.Sensitivity to antitubulin chemotherapeutics is potentiated by a photoactivable nanoliposome[J].Biomaterials,2017,141:50-62.
[9]Giovanella L,Campenni A,Treglia G,et al.Molecular imaging with(99m)Tc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm:a prospective comparison[J].Eur J Nucl Med Mol Imaging,2016,43(6):1018-1026.
[10]Homma T,Manabe O,Ichinokawa K,et al.Breast cancer detected as an incidental finding on99mTc-MIBI scintigraphy[J].Acta Radiol Open,2017,6(7):1-3.
[11]Kurata S,Ushijima K,Kawahara A,et al.Assessment of99mTc-MIBISPECT(/CT)to monitor multidrug resistance-related proteins and apoptosis-related proteins in patients with ovarian cancer:a preliminary study[J].Ann Nucl Med,2015,9(7):643-639.
[12]Kanno S,Utsunomiya K,Kono Y,et al.The effect of radiation exposure on multidrug resistance:in vitro and in vivo studies using nonsmall lung cancer cells[J].EJNMMI Res,2015,5(11):1-9.
[13]Shaw TK,Mandal D,Dey G,et al.Successful delivery of docetaxel to rat brain using experimentally developed nanoliposome:a treatment strategy for brain tumor[J].Drug Deliv,2017,24(1):346-357.
[14]Han Z,Lv L,Ma Y,et al.Cypate-mediated thermosensitive nanoliposome for tumor imaging and photothermal triggered drug release[J].JBiophotonics,2017,10(12):1607-1616.
[15]Yuan J,Zhou X,Cao W,et al.Improved Antitumor Efficacy and Pharmacokinetics of Bufalin via PEGylated Liposomes[J].Nanoscale Res Lett,2017,12(1):585.
[16]Rangsimawong W,Opanasopit P,Rojanarata T,et al.Skin Transport of Hydrophilic Compound-Loaded PEGylated Lipid Nanocarriers:Comparative Study of Liposomes,Niosomes,and Solid Lipid Nanoparticles[J].Biol Pharm Bull,2016,39(8):1254-1262.
[17]Chen Y,Chen J,Cheng Y,et al.A lyophilized sterically stabilized liposome-containing docetaxel:in vitro and in vivo evaluation[J].JLiposome Res,2017,27(1):64-73.
[18]Mo L,Song JG,Lee H,et al.PEGylated hyaluronic acid-coated liposome for enhanced in vivoefficacy of sorafenib via active tumor cell targeting and prolongedsystemic exposure[J].Nanomedicine,2017,14(2):557-567.
[19]刘凤英,于英杰,郑增娟.药物聚乙二醇化的研究进展[J].海峡药学,2016,28(7):1-4.
[20]Wang JP,Zhou XL,Yan JP,et al.Nanobubbles as ultrasound contrast agent for facilitating small cell lung cancer imaging[J].Oncotarget,2017,8(44):78153-78162.