摘要
目的研究肾靶向前体药物雷公藤内酯醇-溶菌酶偶联物的理化性质。方法采用HPLC法考察偶联物在37℃不同pH缓冲液、大鼠血浆及大鼠肾脏溶酶体溶液中的稳定性及细胞毒性。结果体外稳定性试验表明,偶联物在37℃的不同pH缓冲液及大鼠血浆中稳定,在大鼠肾脏溶酶体溶液中可降解。偶联物能降低肾近端小管的细胞毒性,减少脂多糖引导的NO产生。结论雷公藤内酯醇-溶菌酶偶联物可提高雷公藤内酯醇的肾靶向性,并可降低不良反应。
OBJECTIVE To investigate the physicochemical properties of triptolide - lysozyme conjugate for renal targeting delivery. METHODS The concentrations of triptolide in various samples were determined by RP -HPLC. The physicochemical properties and in vitro stability profiles of tfiptolide - lysozyme （TPS - LZM） under various conditions were investigated. RESULTS In vitro release trials showed triptolide -lysozyme was relatively stable in plasma （less than 30% of free triptolide released） and could release triptolide quickly in lysosome（ more than 80% of free tfiptolide released）. In addition, the biological activities of the conjugates on normal rat kidney proximal tubular cells were also tested. CONCLUSION These studies suggest the possibility to promote curative effect and reduce its extra - renal toxicity of triptolide by TPS - LZM conjugates.
出处
《华西药学杂志》
CAS
CSCD
北大核心
2008年第5期505-508,共4页
West China Journal of Pharmaceutical Sciences
基金
国家自然科学基金项目(批准号:30430770)
关键词
溶菌酶
肾靶向
前药
靶向给药系统
Triptolide
Renal drug targeting
Prodrug
Targeted drug delivery system
