史振,夏丹丹,曾光,李雪慧,王绍宁,徐晖
SHI Zhen,XIA Dan-dan,ZENG Guang,LI Xue-hui,WANG Shao-ning,XU Hui

• 1:沈阳药科大学制药工程学院
• 2:沈阳药科大学药学院

摘要(Abstract)：

目的合成药物载体纳米羟基磷灰石(nano-hydroxyapatite,nHAP),考察其对于模型药物阿霉素的载药性能。方法采用化学共沉淀法,以Ca(NO3)2·4H2O和(NH4)2HPO4分别为钙、磷源,用氨水调控溶液p H值合成nHAP,考察温度、反应时间和陈化时间对于nHAP合成的影响。采用X射线衍射仪、扫描电镜、红外光谱仪、动态光散射粒度测定仪对于产品的晶相、晶貌、化学组成和粒径进行表征。采用溶液吸附法考察nHAP用量、溶液质量浓度和p H值对于nHAP负载阿霉素的影响。结果当反应温度60℃、反应时间2 h、陈化时间16 h时,所制备的nHAP为长(138±35)nm,宽(39±8)nm棒状纳米粒,晶体形貌规则,结晶良好。负载阿霉素的研究表明,所合成的nHAP载药性能良好,载药量达到42.43 mg·g~(-1)。结论 nHAP对于阿霉素具有良好的承载能力,可作为阿霉素的优良载体。
Objective To synthesis nano-hydroxyapatite(nHAP) as drug carrier and investigate the drug loading properties for doxorubicin.Methods Chemical co-precipitation method was used to synthesis nHAP with[Ca(NO_3)_2·4H_2O]and [(NH_4)_2HPO_4]as the sources of calcium and phosphorus,respectively.The pH of reactive system was controlled by addition of ammonia.Factors affecting the formation of nHAP crystals were evaluated,such as temperature,reaction time,aging time.The crystal phase,crystal morphology,chemical composition,particle size of the obtained crystals were characterized by using X-ray diffraction,scanning electron microscopy,infrared spectrometry and laser particle size tester.Doxorubicin(DOX·HCl) was loaded to nHAP by solution absorption method,and the influences of nHAP amount,concentration of DOX·HCl and p H value on the drug loading were investigated.Results The sample of nHAP obtained at the optimum process condition with temperature at 60 ℃,reaction time of 2 h,aging time of 16 h,was rod-like with a length of(138 ± 35) nm and a width of(39 ± 8) nm.Meanwhile,the crystals had uniform morphology and fine crystallinity.Synthesized nHAP was shown to have a good capacity for adsorbing DOX·HCl with the drug loading of 42.43 mg·g~(-1).Conclusions nHAP can be used as a potential drug carrier.

关键词(KeyWords)： 纳米羟基磷灰石;化学共沉淀;阿霉素;载药
nano-hydroxyapatite;chemical co-precipitation;doxorubicin;drug loading

Abstract:

Keywords:

基金项目(Foundation): 辽宁省教育厅科学技术研究项目(L2014395);; 沈阳药科大学国家级大学生创新创业训练计划项目(201510163025)

作者(Author): 史振,夏丹丹,曾光,李雪慧,王绍宁,徐晖
SHI Zhen,XIA Dan-dan,ZENG Guang,LI Xue-hui,WANG Shao-ning,XU Hui

DOI: 10.14066/j.cnki.cn21-1349/r.2017.01.001

参考文献(References)：

• [1]MEHDI S S,MOHAMMAD T K,EHSAN D K,et al.Synthesis methods for nanosized-hydroxyapatite with diverse structures[J].Acta Biomater,2013,9:7591-7621.
• [2]WANG S,WANG X,XU H,et al.Towards sustained delivery of small molecular drugs using hydroxyapatite microspheres as the vehicle[J].Advanced Powder Technology,2010,21(3):268-272.
• [3]YANG P,QUAN Z,LI C,et al.Bioactive,luminescent and mesoporous europium-doped hydroxyapatite as a drug carrier[J].Biomaterials,2008,29(32):4341-4347.
• [4]BARROUG A,GLIMCHER M.Hydroxyapatite crystals as a local delivery system for cisplatin:adsorption and release of cisplatin in vitro[J].Journal of Orthopaedic Research,2002,20(2):274-280.
• [5]MAVROPOULOS E,COSTA A M,COSTA L T,et al.Adsorption and bioactivity studies of albumin onto hydroxyapatite surface[J].Colloids&Surfaces B Biointerfaces,2011,83(1):1-9.
• [6]赵勤富,郑力,王思玲.纳米多孔羟基磷灰石的制备方法及其在药物载体方面应用的研究进展[J].沈阳药科大学学报,2010,27(12):1009-1013.
• [7]WANG P,LI C,GONG H,et al.Effects of synthesis conditions on the morphology of hydroxyapatite nanoparticles produced by wet chemical process[J].Powder Technology,2010,203(2):315-321.
• [8]ZHANG G,CHEN J,YANG S,et al.Preparation of amino-acid-regulated hydroxyapatite particles by hydrothermal method[J].Materials Letters,2011,65(3):572-574.
• [9]PADMANABHAN S K,BALAKRISHNAN A,CHU M C,et al.Sol-gel synthesis and characterization of hydroxyapatite nanorods[J].Particuology,2009,7(6):466-470.
• [10]LI H,ZHU M Y,LI L H,et al.Processing of nanocrystalline hydroxyapatite particles via reverse microemulsions[J].Journal of Materials Science,2008,43(1):384-389.
• [11]THI T T P,PHUONG N T,PHAM T N,et al.Impact of physical and chemical parameters on the hydroxyapatite nanopowder synthesized by chemical precipitation method[J].Advances in Natural Sciences Nanoscience&Nanotechnology,2013,4(3):035014.
• [12]BROWN W E,CHOW L C.Combinations of sparingly soluble calcium phosphates in slurries and pastes as mineralizers and cements:US,US RE33161 E[P].1990-02-06.
• [13]郭连峰,张文光,王成焘.纳米羟基磷灰石的制备及结晶尺寸的控制[J].无机化学学报,2004,20(3):291-296.
• [14]利物浦大学.Chem Tube 3D[EB/OL].[2016-04-26].http://chemtube3d.com/index.html.
• [15]KAWASAKI T,NIIKURA M,KOBAYASHI Y.Fundamental study of hydroxyapatite high-performance liquid chromatography:III.Direct experimental confirmation of the existence of two types of adsorbing surface on the hydroxyapatite crystal[J].Journal of Chromatography A,1990,515:125-148.
• [16]Copper(II)-anthracycline systems.Evidence of a dihydroxo-bridged dicopper(II)aclacinomycin complex[J].Journal of Inorganic Biochemistry,1987,31(1):43-55.