丙氨瑞林微球的体外释放
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国家自然科学基金(81000689,81172514,30873178),上海市自然科学基金(10ZR1437300).


In vitro release of alarelin-loaded microspheres
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Supported by National Natural Science Foundation of China (81000689, 81172514, 30873178) and Natural Science Foundation of Shanghai(10ZR1437300).

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    摘要:

    目的研究不同内水相明胶浓度、不同微球挥干固化方法和不同pH值释放介质等对丙氨瑞林微球的体外释放趋势的影响。方法由溶剂挥发法-复乳法(W/O/W)制备丙氨瑞林微球,内水相分别采用0%、8%、16%明胶水溶液,使用室温常压挥发和低温真空挥发法固化微球。体外释放实验中,采用pH=4.5、pH=7.0、pH=10.0三种释放介质,于第1、7、14、21、28、35天取样,残余法测定体外释放微球突释量及释放度,使用电子扫描电镜记录微球释放期间各取样点的微球降解程度。结果有机溶剂挥发固化方法会影响微球的体外释放模式,含不同明胶浓度内水相的微球有不同的体外释放模式,微球中的丙氨瑞林在释放介质pH=10.0中释放速率最快,而在pH=4.5中不能完全释放,最适宜的释放介质是pH=7.0缓冲液。结论不同挥发固化方法制备会影响微球的突释量,但对微球的整体体外释放趋势没有影响,内水相浓度对体外释放的趋势有影响,释放介质的pH值对丙氨瑞林微球药物的释放有影响。

    Abstract:

    ObjectiveTo study the influence of different evaporation hardening methods, gelatin concentrations in inter aqueous phase and pH values of PBS on in vitro release modulus of alarelin-loaded microspheres (AR-MS). MethodsThe AR-MS was prepared by double emulsion solvent evaporation method (W/O/W); concentrations of internal aqueous phase with gelatin were 0%, 8% and 16% (W/V); and the volatilized hardening was done with room temperature magnetic stirring and low-temperature vacuum evaporation. Residual method assay was used to determine the accumulated release and burst release of AR-MS in PBS (pH = 4.5, pH = 7.0, pH = 10.0) on day 1, 7, 14, 21, 28, and 35. Scanning electron microscopy (SEM) was used to observe the degradation degrees of AR-MS at each time point. ResultsThe method of volatized organic solvents could affect the release pattern of AR-MS, and the release pattern was also influenced by different concentrations of internal aqueous phase of gelatin. The fastest release rate of AR-MS was seen in medium with pH value being 10.0, complete release was not found in medium with pH being 4.5, and the most appropriate medium for AR-MS release was when pH value being 7.0. ConclusionDifferent evaporation hardening methods can influence the burst release of AR-MS, but has no influence on the overall in vitro release pattern. Different concentrations of internal aqueous gelatin phase can influence the in vitro release pattern, and the medium pH value can also influence the release of AR-MS.

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  • 收稿日期:2012-05-02
  • 最后修改日期:2012-08-27
  • 录用日期:2012-09-06
  • 在线发布日期: 2012-09-24
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