摘要
目的合成地塞米松缓释剂,探讨局部应用地塞米松的可行性。方法采用国外进口乳酸-聚羟基乙酸共聚物(PLGA),以溶解挥发法制备PLGA-地塞米松缓释剂。体外进行PLGA-地塞米松微球载药率测定,从而得到合适浓度的微球,继而制成10mg和4mg两种规格的缓释片,并对缓释片的载药率进行筛选。将制成的缓释片植于大鼠颅内,经高压液相法测定出不同部位及不同时间的脑组织药物释放率。结果制得的PLGA-地塞米松微球中地塞米松磷酸钠(DSP)的载药量为6.1%(W/W)。DSP-PLGA缓释微球10mg片第1个小时释放出130μgDSP,之后释放速率趋向平稳,至第7天仍有20μg/d释出;4mg片第1个小时释出40μgDSP,至第7天仍有少量释出。10mg缓释片组体内释放实验结果显示:1,2,6,24,72和168h脑内药物含量分别为38.49,21.34,16.72,11.52,6.31和0.51μg/g。结论PLGA可以很好地缓慢控释地塞米松;在脑内局部应用DSP-PLGA,可以得到较高的局部有效药物浓度,并被脑组织很好地耐受。
Objective To synthesize the slow-release dexamethasone, and investigate the feasibility of its partially application. Methods Solvent evaporation method was used to make DSP （Dexamethasone sodium phosphate）-PLGA （polylactic-co-glycolic acid） polymer. In vitro the loading ratio was measured and got the appropriated concentration. The 10mg and 4mg polymer tablets were made. After the selection of the tablets concentration, the tablets were delivered to rat brain and the releasing rate at different areas and different time in the brain was measured by high performance liquid chromatography （HPLC）. Results The loading rate ofdexamethasone sodium phosphate is 6.1% （W/W）. The first hour releasing of 10mg DSP-PLGA tablets was 130μg, after then the releasing rate got placidity. There are 20μg/d DSP was released up to the 7th day. The first hour releasing of4mg DSP-PLGA tablets was 401xg, and there still remain some at the 7th day. In vivo the 10mg DSP-PLGA tablets got 38.49, 21.34, 16.72, 11.52, 6.31 and 0.51μg/g remain in the brain tissue after 1, 2, 6, 24, 72 and 168hs releasing. Conclusion PLGA can control the releasing of dexamethasone well. A very high local concentration can be got by local brain delivering of DSP-PLGA. It can be tolerated well by the brain and has potential mean for a new way of local application of dexamethasone.
出处
《中国微侵袭神经外科杂志》
CAS
2006年第7期324-326,共3页
Chinese Journal of Minimally Invasive Neurosurgery
