摘要
目的研究和克服胰岛素在电致孔下经皮传输过程中在皮肤中的滞留,提高胰岛素的经皮渗透速率。方法体外实验,裸鼠皮肤。采用荧光标记的手段研究胰岛素在皮肤中的滞留情况,使用表面活性剂十六烷基三甲基溴化铵(CTAB)阻止胰岛素的聚集,减少药物在皮肤中的滞留。结果超过50%的胰岛素在电致孔经皮传输的过程中滞留于皮肤中,滞留量随脉冲时间常数的减小和胰岛素浓度的增加而增加;滞留胰岛素在再次进行脉冲时可部分的释放,但是活性明显下降。在供给液中加入CTAB,其与胰岛素的物质的量之比为15时,胰岛素滞留减小20%,电致孔时的经皮渗透速率提高1倍多。结论胰岛素在皮肤中的积累是限制其在电致孔下经皮传输速率的主要原因之一,通过阻止分子聚集和疏通LTRs的方法可以减小药物的滞留,提高经皮传输速率。
OBJECTIVE: To investigate the entrapment of insulin in skin via electroporation, diminish the entrapment and enhance the transdermal delivery of insulin. METHODS: The entrapment of insulin in skin during skin electroporation was investigated using nude mouse skin and FITC-labeled-insulin in vitro. Ionic surfactant, CTAB, was used to inhibit the self-association of insulin and to diminish the entrapment of insulin in skin. RESULTS: Over 50% insulin was entrapped in skin during transdermal delivery, and more insulin was entrapped with the shorter pulses and higher concentration of insulin in the solution. Entrapped insulin was partly released when another group of pulses was applied, and the bioactivity of insulin was reduced. When the molar ratio of CTAB to insulin was 15 in the solution, the amount of entrapped insulin was reduced by 20% and transdermal delivery rate during electroporation was increased by more than one fold. CONCLUSION: The entrapment of insulin in skin is one of the cardinal resistances for the transdermal delivery of insulin via electroporation. The entrapment can be attenuated by inhibiting the self-association of molecules and reducing the sinuosity of LTRs. Thus, the transdermal delivery rate is increased.
出处
《中国药学杂志》
EI
CAS
CSCD
北大核心
2005年第7期525-528,共4页
Chinese Pharmaceutical Journal
基金
国家自然科学基金(20376038)教育部高校博士点基金(20020003056)
