温度敏感性脂质体包裹磁性阿霉素纳米粒的制备及其物理性质的研究
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摘要
目的制备具有稳定磁性、能够携带化疗药物的温度敏感性脂质体磁性纳米粒,并对纳米粒的粒径大小、初步磁性、药物包裹率、稳定性、和温度控释性等物理性质进行检测。
方法以化学共沉淀法制备四氧化三铁纳米粒,以逆相蒸发法制备空白温度敏感性磁性脂质体纳米粒,梯度反向装载法包封阿霉素药物,以外加磁场初步检测最终产物磁性,激光粒度分析仪检测粒径大小分布范围,透射电镜观察粒子形态；酸性乙醇荧光分光光度法测量阿霉素包裹率和泄漏率,同时以热敏释放百分率观察温度控释特性。
结果制备的温度敏感性脂质体磁性纳米粒平均粒径为(76±18)nm,粒径较均匀,粒子表现出磁性,平均包裹率为(42.6±0.7)%,室温下贮存稳定,具有敏感的温度控释特性。
结论本实验制备的温度敏感性脂质体磁性纳米粒基本符合要求,为进一步研究提供了基础。
Objective:To prepare thermo-sensitive-liposome-magnetic-adriamycin-nanoparticles (Ts-LMADM), measure physical property of the Ts-LMADM, such as size of nanospheres, magnetism, content of ADM, drug loading (DL), thermo-controlled drug-release characteristic and stability.
Methods:Four iron oxide nanoparticles were prepared by chemical coprecipitation method, blank thermo-sensitive-liposome-magnetic-nanoparticles were prepared by reverse-phase evaporation method, doxorubicin was encapsulated in the nanoparticles by reverse gradient loading method, the magnetism of end product was detected in the magnetic field, particle size distribution range was detected by laser particle size analyzer, particles' morphology was observed by transmission electron microscopy, encapsulated rate and leakage rate of doxorubicin in the nanoparticles were mesured by acidic ethanol fluorescence spectrophotometry, thermo-controlled-release property of the nanoparticles was observed by percentage of release at different temperature.
Results:The thermo-sensitive-liposome-magnetic-adriamycin-nanoparticles prepared is uniform, with average size (76±18) nm and average encapsulated rate (42.6±0.7)%, showing magnetism, stability at room temperature, and sensitive thermo-controlled-release properties.
Conclusion:In this study, the thermo-sensitive-liposome-magnetic- adriamycin-nanoparticles prepared basically meet the requirements for further study.
方法以化学共沉淀法制备四氧化三铁纳米粒,以逆相蒸发法制备空白温度敏感性磁性脂质体纳米粒,梯度反向装载法包封阿霉素药物,以外加磁场初步检测最终产物磁性,激光粒度分析仪检测粒径大小分布范围,透射电镜观察粒子形态；酸性乙醇荧光分光光度法测量阿霉素包裹率和泄漏率,同时以热敏释放百分率观察温度控释特性。
结果制备的温度敏感性脂质体磁性纳米粒平均粒径为(76±18)nm,粒径较均匀,粒子表现出磁性,平均包裹率为(42.6±0.7)%,室温下贮存稳定,具有敏感的温度控释特性。
结论本实验制备的温度敏感性脂质体磁性纳米粒基本符合要求,为进一步研究提供了基础。
Objective:To prepare thermo-sensitive-liposome-magnetic-adriamycin-nanoparticles (Ts-LMADM), measure physical property of the Ts-LMADM, such as size of nanospheres, magnetism, content of ADM, drug loading (DL), thermo-controlled drug-release characteristic and stability.
Methods:Four iron oxide nanoparticles were prepared by chemical coprecipitation method, blank thermo-sensitive-liposome-magnetic-nanoparticles were prepared by reverse-phase evaporation method, doxorubicin was encapsulated in the nanoparticles by reverse gradient loading method, the magnetism of end product was detected in the magnetic field, particle size distribution range was detected by laser particle size analyzer, particles' morphology was observed by transmission electron microscopy, encapsulated rate and leakage rate of doxorubicin in the nanoparticles were mesured by acidic ethanol fluorescence spectrophotometry, thermo-controlled-release property of the nanoparticles was observed by percentage of release at different temperature.
Results:The thermo-sensitive-liposome-magnetic-adriamycin-nanoparticles prepared is uniform, with average size (76±18) nm and average encapsulated rate (42.6±0.7)%, showing magnetism, stability at room temperature, and sensitive thermo-controlled-release properties.
Conclusion:In this study, the thermo-sensitive-liposome-magnetic- adriamycin-nanoparticles prepared basically meet the requirements for further study.
引文
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[6]钭启升,张辉，邬剑波,等.氧化铁和羟基氧化铁纳米结构的水热法制备及其表征[J].无机材料学报,2007,22(2)：213-218.
[7]张秋禹,张和鹏,张军平,等.反相微乳液法制备纳米氧化铁颗粒的结构及性能[J].过程工程学报,2006,z2：276-279.
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[12]Hassan EE, Parish RC, Gallo JM. Optimized formulation of magnetic chitosan microspheres containing the anticancer agent, oxantrazole[J]. Pharm Res,1992,9: 390.
[13]Widder KJ. In vitor release of biologically active adriamycin by magneticell responsive album microspheres[J]. Cancer Res,1980,40:3512-3517.
[14]陈道达,艾时斌,马建华,等.磁液载附阿霉素靶向定位治疗消化系肿瘤[J].中华实验外科杂志,1996,13：1-2.
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[17]Widder KJ, Morino PA, Morris PM. Selective targeting of magnetic albumin microspheres to the Yoshida sarcoma:ultrastructural evaluation of microsphere disposition[J]. Eur J Cancer Clin Oncol[J].1983,19(1):141-147.
[18]张阳德,龚连生.磁性阿霉素白蛋白纳米粒的研制[J].中国现代医学杂志2001,11(3)：1-4.
[19]韦勇强,赖琼钰.磁性液体的合成及生物医学应用[J].化学研究与应用,2003,15(3)：307-310.
[20]贾秀鹏,张东生.磁流体在肿瘤学治疗领域的应用进展[J].国外医学肿瘤学分册2002,29(3)：187-190.
[21]Pankhurst QA, Connolly J, Jones SK, et al. Applications of magnetic nanoparticles in biomedicine[J]. J Phys D:Appl Phys,2003,36:R167.
[22]Berry CC, Curtis ASG. Functionalisation of magnetic nanoparticles for applications in biomedicine[J]. J Phys D:Appl Phys,2003,36:r198.
[23]Tang ZY, Ye TQ, Zhou XD, et al. The changing vale of surgery in the treatment of primary liver cancer[J]. Sermin Surg Oncol,1988,2:103
[24]朱 峰,周新腾.一种新型脂质体-热敏脂质体[J].中国医药报,2002,11(4)：243-247.
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