载地塞米松中空碳羟基磷灰石微球的合成与体外释放研究
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摘要
目的制备碳羟基磷灰石中空微球,构建地塞米松药物缓释系统,为其作为活髓保存剂应用于临床提供实验数据。方法以甘氨酸(Gly)和十二烷基磺酸钠(SDS)组成的"核-壳"式复合物为模板,合成碳羟基磷灰石中空微球。利用场发射扫描电镜(FESEM)、高分辨透射电子显微镜(HRTEM)、X射线衍射仪(XRD)、氮气吸附脱附分析(BET)分别对其形貌、物相、比表面积及孔径进行表征分析。通过与无Gly组对比,探讨中空微球的形成机理。将地塞米松载入碳羟基磷灰石中空微球构成体外缓释系统,计算载药率、包封率和药物体外缓释时间。结果成功制备直径为2~4μm针状中空碳羟基磷灰石微球,该微球具有良好的载药性(载药率12.1%~34.8%)和体外药物缓释性能,缓慢释放达30天,几乎无突释现象。结论合成的碳羟基磷灰石中空微球类似骨和牙齿的无机物主要组成成分,载药率和包封率均较高,微球中药物缓慢释放接近线性。
Objective To prepare hollow carbonated hydroxyapatite microspheres loaded with dexamethasone to develop a drug delivery system,thereby laying the scientific foundation for the clinical application of preservative for live pulp.Methods Hollow microspheres of carbon-hydroxyapatite were synthesized by using the "core-shell" complex of glycine(Gly) and sodium dodecyl sulfate(SDS).The morphology,phase,specific surface area and pore size were characterized by FESEM,HRTEM,XRD and BET,respectively.By comparing to the Gly-free group,the formation mechanism of hollow microspheres was explored.Dexamethasone was loaded into hollow carbonated hydroxyapatite microspheres to form an in vitro sustained-release system.The drug-loading rate,encapsulationt efficiency and drug sustained-release time in vitro were calculated.Results The prepared hydroxyapatite was a hollow microsphere composed of acicular nanoparticles with a diameter of 2-4 μm.The hollow microspheres showed a good drug loading(drug loading rate of 12.1%~34.8%) effect and the release of dexamethasone initially increased linearly with time,with sustained release having been achieved for almost 30 days with minimal burst phenomenon.Conclusion Hollow carbonated hydroxyapatite microspheres,similar to the main inorganic components of bone and tooth,can be synthesized by using the organic matter(Gly) and the surfactant(SDS) as template.Loading rate and encapsulation efficiency of the drug are high,and in vitro release of the drug is nearly linear.
Objective To prepare hollow carbonated hydroxyapatite microspheres loaded with dexamethasone to develop a drug delivery system,thereby laying the scientific foundation for the clinical application of preservative for live pulp.Methods Hollow microspheres of carbon-hydroxyapatite were synthesized by using the "core-shell" complex of glycine(Gly) and sodium dodecyl sulfate(SDS).The morphology,phase,specific surface area and pore size were characterized by FESEM,HRTEM,XRD and BET,respectively.By comparing to the Gly-free group,the formation mechanism of hollow microspheres was explored.Dexamethasone was loaded into hollow carbonated hydroxyapatite microspheres to form an in vitro sustained-release system.The drug-loading rate,encapsulationt efficiency and drug sustained-release time in vitro were calculated.Results The prepared hydroxyapatite was a hollow microsphere composed of acicular nanoparticles with a diameter of 2-4 μm.The hollow microspheres showed a good drug loading(drug loading rate of 12.1%~34.8%) effect and the release of dexamethasone initially increased linearly with time,with sustained release having been achieved for almost 30 days with minimal burst phenomenon.Conclusion Hollow carbonated hydroxyapatite microspheres,similar to the main inorganic components of bone and tooth,can be synthesized by using the organic matter(Gly) and the surfactant(SDS) as template.Loading rate and encapsulation efficiency of the drug are high,and in vitro release of the drug is nearly linear.
引文
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3 Liu J,Huang Y,Kumar A,et al.p H-sensitive nano-systems for drug delivery in cancer therapy.Biotechnology advances,2014,32(4):693-710.
4轩和.地塞米松药物相互作用研究进展.中国医药报,2004-07-06.
5 Zhou X,Feng W,Qiu K,et al.BMP-2 derived peptide and dexamethasone incorporated mesoporous silica nanoparticles for enhanced osteogenic differentiation of bone mesenchymal stem cells.ACS applied materials&interfaces,2015,7(29):15777-89.
6 Alliot-Licht B,Bluteau G,Magne D,et al.Dexamethasone stimulates differentiation of odontoblast-like cells in human dental pulp cultures.Cell and tissue research,2005,321(3):391-400.
7 Mousavi SA,Ghoddusi J,Mohtasham N,et al.Human pulp response to direct pulp capping and miniature pulpotomy with MTA after application of topical dexamethasone:a randomized clinical trial.Iranian endodontic journal,2016,11(2):85.
8 Abdallah M-N,Eimar H,Bassett DC,et al.Diagenesis-inspired reaction of magnesium ions with surface enamel mineral modifies properties of human teeth.Acta biomaterialia,2016,37:174-83.
9 Sing KS.Reporting physisorption data for gas/solid systems with special reference to the determination of surface area and porosity(Recommendations 1984).Pure and applied chemistry,1985,57(4):603-19.
10 Lai W,Chen C,Ren X,et al.Hydrothermal fabrication of porous hollow hydroxyapatite microspheres for a drug delivery system.Materials science&engineering:C,2016,62:166-72.
11 Wang K,Wang Y,Zhao X,et al.Sustained release of simvastatin from hollow carbonated hydroxyapatite microspheres prepared by aspartic acid and sodium dodecyl sulfate.Materials Science and Engineering:C,2017,75:565-71.
12 Miura M,Kodama M.The second CMC of the aqueous solution of sodium dodecyl sulfate.I.Conductivity.Bulletin of the Chemical Society of Japan,1972,45(2):428-31.
13 Tong H,Ma W,Wang L,et al.Control over the crystal phase,shape,size and aggregation of calcium carbonate via a l-aspartic acid inducing process.Biomaterials,2004,25(17):3923-3929.
14 Westin K J,Rasmuson?C.Nucleation of calcium carbonate in presence of citric acid,DTPA,EDTA and pyromelliticacid.Journal of colloid and interface science,2005,282(2):370-379.
2 Fu H,Rahaman MN,Brown RF,et al.Evaluation of BSAprotein release from hollow hydroxyapatite microspheres into PEG hydrogel.Materials Science and Engineering:C,2013,33(4):2245-50.
3 Liu J,Huang Y,Kumar A,et al.p H-sensitive nano-systems for drug delivery in cancer therapy.Biotechnology advances,2014,32(4):693-710.
4轩和.地塞米松药物相互作用研究进展.中国医药报,2004-07-06.
5 Zhou X,Feng W,Qiu K,et al.BMP-2 derived peptide and dexamethasone incorporated mesoporous silica nanoparticles for enhanced osteogenic differentiation of bone mesenchymal stem cells.ACS applied materials&interfaces,2015,7(29):15777-89.
6 Alliot-Licht B,Bluteau G,Magne D,et al.Dexamethasone stimulates differentiation of odontoblast-like cells in human dental pulp cultures.Cell and tissue research,2005,321(3):391-400.
7 Mousavi SA,Ghoddusi J,Mohtasham N,et al.Human pulp response to direct pulp capping and miniature pulpotomy with MTA after application of topical dexamethasone:a randomized clinical trial.Iranian endodontic journal,2016,11(2):85.
8 Abdallah M-N,Eimar H,Bassett DC,et al.Diagenesis-inspired reaction of magnesium ions with surface enamel mineral modifies properties of human teeth.Acta biomaterialia,2016,37:174-83.
9 Sing KS.Reporting physisorption data for gas/solid systems with special reference to the determination of surface area and porosity(Recommendations 1984).Pure and applied chemistry,1985,57(4):603-19.
10 Lai W,Chen C,Ren X,et al.Hydrothermal fabrication of porous hollow hydroxyapatite microspheres for a drug delivery system.Materials science&engineering:C,2016,62:166-72.
11 Wang K,Wang Y,Zhao X,et al.Sustained release of simvastatin from hollow carbonated hydroxyapatite microspheres prepared by aspartic acid and sodium dodecyl sulfate.Materials Science and Engineering:C,2017,75:565-71.
12 Miura M,Kodama M.The second CMC of the aqueous solution of sodium dodecyl sulfate.I.Conductivity.Bulletin of the Chemical Society of Japan,1972,45(2):428-31.
13 Tong H,Ma W,Wang L,et al.Control over the crystal phase,shape,size and aggregation of calcium carbonate via a l-aspartic acid inducing process.Biomaterials,2004,25(17):3923-3929.
14 Westin K J,Rasmuson?C.Nucleation of calcium carbonate in presence of citric acid,DTPA,EDTA and pyromelliticacid.Journal of colloid and interface science,2005,282(2):370-379.