内疏水型复合中空微球的制备与药物缓释性能研究
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摘要
近年来,由于药物缓释技术在现代医药中具重要作用,其应用越来越广泛。无机中空微球由于其特有的内部空腔和多孔结构,良好的稳定性,表面易于修饰改性等特点,使其在药物缓释领域具有良好的应用前景。为了得到载药量大,生物相容性好,结构稳定,并具有良好的缓释效果的新型药物载体,本论文制备了多种具有内部疏水、外部亲水结构的复合无机氧化物中空微球,并考察了其药物缓释性能。
1.制备了内疏水SiO2/TiO2复合中空微球。以碳酸钙微球为模板,制备了SiO2中空微球；然后采用十八烷基三甲氧基硅烷对SiO2中空微球进行疏水改性(SiO2-C18),接着在SiO2-C18表而吸附一层卵磷脂(SiO2-C18-PC)进行亲水转换,最后在SiO2-C18-PC表面包覆一层完整的二氧化钛得到SiO2-C18-PC/TiO2中空微球(记为内疏水SiO2/TiO2复合中空微球),得到内疏水、外亲水SiO2/TiO2复合中空微球。电镜和氮气吸附/脱附结果表明它具有完整的空腔结构和多孔的壳层结构,而且孔径分布良好。以脂溶性药物布洛芬为对象,考察了SiO2-C18-PC/TiO2的药物缓释效果,结果表明：由于中空材料内部空腔表面键合有疏水长链,它对脂溶性药物有一定的浓缩、萃取作用,因此,载药量增大；同时,疏水作用也降低了药物的释放速率,使其具有良好的缓释效果。
2.制备了内疏水SiO2/Fe3O4复合中空微球。通过在SiO2-C18-PC表面包覆一层完整的Fe3O4壳层,得到SiO2-C18-PC/Fe3O4中空微球(记为内疏水SiO2/Fe3O4复合中空微球),不仅可以使外表面的亲水层得到了进一步的固化,而且还让材料具有磁性。以脂溶性药物布洛芬为对象,分别考察了SiO2-C18-PC/Fe3O4的药物缓释性能,实验结果证明：磁性复合材料SiO2-C18-PC/Fe3O4有良好的药物缓释性能。
3.为深入探讨不同的转换剂及无机包覆层对缓释性能的影响,制备了SiO2-C18-C18/SiO2中空微球,分别采用卵磷脂、CTAB和硅烷偶联剂(C18)作为亲水转化剂对SiO2-C18表面进行了亲水转化,考察了不同的转换剂对无机层包覆效果的影响,结果表明以C18作为亲水转化剂具有较好的转换和包覆效果。
Recently, drug slow releasing technology has become to be a important role in the modern medicine. But it is always difficult to control the release of drug. Inorganic hollow microspheres drug slow-release has a lot of field application prospect due to its unique internal cavity and porous structure, good stability, and the surface is easy to modify modification. In order to obtain the new drug carrier which have a big drug loading, good biocompatibility, stability analysis of structures and good slow-release effect. Therefore, hollow microspheres with hydrophobic inner surface and hydrophilic surface are synthesized. And the magnetic targeted materials are also synthesized in this paper. Herein, their drug release behaviors have been investigated.
1. Prepared the SiO2-C18-PC/TiO2hollow spheres. Using calcium carbonate microspheres as templates, prepared SiO2hollow microspheres. SiO2hollow spheres were modified by18alkyl methylerichlorosilane (SiO2-C18), Then the surface of the SiO2-C18adsorb a layer of lecithin(SiO2-C18-PC), Finally the surface of SiO2-C18-PC coating a layer of complete titanium dioxide (SiO2-C18-PC/TiO2), achieve its external surface close water conversion. Electron microscopy and nitrogen adsorption/desorption results show that it has a complete cavity structure and porous shell structure, and have a good hole size distribution. Using fat-soluble ibuprofen (IBU) as a model drug, the investigation of drug release rates of the SiO2-C18-PC/TiO2shows that SiO2-C18-PC/TiO2have a good drug slow-release effect due to introduction of hydrophobic groups, as they have certain adsorption reaction with the hydrophobic drug, which let the release rate slower.
2. Prepared the SiO2-C18-PC/Fe3O4hollow spheres. Using SiO2-C18-PC as templates, coating a layer of complete Fe3O4shell in different way. It was not only can make the close water appearance get further solidify, but also let it with magnetic ability which has a good application prospect in the field of targeted drug release. Using fat-soluble ibuprofen(IBU) as a model, the investigation of drug release rates of the SiO2-C18-PC/Fe3O4shown that the modified SiO2-C18-PC/Fe3O4exhibit lower release rate due to the hydrophobic effect.
3. For further study the effect of the selective modification on drug release, SiO2-C18-C18/SiO2hollow spheres have been synthesized. Using different kinds of amphoteric molecules(PC、CTAB、C18) as the hydrophilic convert agent, the investigation of the experimental results show that use C18as the convert agent, have a wonderful transformation effect and inorganic layer coated effect.
1.制备了内疏水SiO2/TiO2复合中空微球。以碳酸钙微球为模板,制备了SiO2中空微球；然后采用十八烷基三甲氧基硅烷对SiO2中空微球进行疏水改性(SiO2-C18),接着在SiO2-C18表而吸附一层卵磷脂(SiO2-C18-PC)进行亲水转换,最后在SiO2-C18-PC表面包覆一层完整的二氧化钛得到SiO2-C18-PC/TiO2中空微球(记为内疏水SiO2/TiO2复合中空微球),得到内疏水、外亲水SiO2/TiO2复合中空微球。电镜和氮气吸附/脱附结果表明它具有完整的空腔结构和多孔的壳层结构,而且孔径分布良好。以脂溶性药物布洛芬为对象,考察了SiO2-C18-PC/TiO2的药物缓释效果,结果表明：由于中空材料内部空腔表面键合有疏水长链,它对脂溶性药物有一定的浓缩、萃取作用,因此,载药量增大；同时,疏水作用也降低了药物的释放速率,使其具有良好的缓释效果。
2.制备了内疏水SiO2/Fe3O4复合中空微球。通过在SiO2-C18-PC表面包覆一层完整的Fe3O4壳层,得到SiO2-C18-PC/Fe3O4中空微球(记为内疏水SiO2/Fe3O4复合中空微球),不仅可以使外表面的亲水层得到了进一步的固化,而且还让材料具有磁性。以脂溶性药物布洛芬为对象,分别考察了SiO2-C18-PC/Fe3O4的药物缓释性能,实验结果证明：磁性复合材料SiO2-C18-PC/Fe3O4有良好的药物缓释性能。
3.为深入探讨不同的转换剂及无机包覆层对缓释性能的影响,制备了SiO2-C18-C18/SiO2中空微球,分别采用卵磷脂、CTAB和硅烷偶联剂(C18)作为亲水转化剂对SiO2-C18表面进行了亲水转化,考察了不同的转换剂对无机层包覆效果的影响,结果表明以C18作为亲水转化剂具有较好的转换和包覆效果。
Recently, drug slow releasing technology has become to be a important role in the modern medicine. But it is always difficult to control the release of drug. Inorganic hollow microspheres drug slow-release has a lot of field application prospect due to its unique internal cavity and porous structure, good stability, and the surface is easy to modify modification. In order to obtain the new drug carrier which have a big drug loading, good biocompatibility, stability analysis of structures and good slow-release effect. Therefore, hollow microspheres with hydrophobic inner surface and hydrophilic surface are synthesized. And the magnetic targeted materials are also synthesized in this paper. Herein, their drug release behaviors have been investigated.
1. Prepared the SiO2-C18-PC/TiO2hollow spheres. Using calcium carbonate microspheres as templates, prepared SiO2hollow microspheres. SiO2hollow spheres were modified by18alkyl methylerichlorosilane (SiO2-C18), Then the surface of the SiO2-C18adsorb a layer of lecithin(SiO2-C18-PC), Finally the surface of SiO2-C18-PC coating a layer of complete titanium dioxide (SiO2-C18-PC/TiO2), achieve its external surface close water conversion. Electron microscopy and nitrogen adsorption/desorption results show that it has a complete cavity structure and porous shell structure, and have a good hole size distribution. Using fat-soluble ibuprofen (IBU) as a model drug, the investigation of drug release rates of the SiO2-C18-PC/TiO2shows that SiO2-C18-PC/TiO2have a good drug slow-release effect due to introduction of hydrophobic groups, as they have certain adsorption reaction with the hydrophobic drug, which let the release rate slower.
2. Prepared the SiO2-C18-PC/Fe3O4hollow spheres. Using SiO2-C18-PC as templates, coating a layer of complete Fe3O4shell in different way. It was not only can make the close water appearance get further solidify, but also let it with magnetic ability which has a good application prospect in the field of targeted drug release. Using fat-soluble ibuprofen(IBU) as a model, the investigation of drug release rates of the SiO2-C18-PC/Fe3O4shown that the modified SiO2-C18-PC/Fe3O4exhibit lower release rate due to the hydrophobic effect.
3. For further study the effect of the selective modification on drug release, SiO2-C18-C18/SiO2hollow spheres have been synthesized. Using different kinds of amphoteric molecules(PC、CTAB、C18) as the hydrophilic convert agent, the investigation of the experimental results show that use C18as the convert agent, have a wonderful transformation effect and inorganic layer coated effect.
引文
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