摘要
目的制备9-硝基喜树碱(9-nitrocamptothecin,9-NC)自乳化微乳(自微乳),并考察其对9-NC内酯型的体内外保护效应。方法以油酸乙酯为油相,Cremophor EL或Tween 80为乳化剂,PEG-400和无水乙醇为助乳化剂,制得2种9-NC自微乳。以9-NC溶液剂为对照,考察自微乳对9-NC内酯型结构的体内外保护效应。结果分别以Cremophor EL和Tween 80为乳化剂的自乳化油(油相-乳化剂-助乳化剂=20∶40∶40)在稀释倍数为20倍的水相中均可自发形成O/W型微乳液(9-NCME-C或9-NCME-T),粒径分别为(30.2±4.6)和(21.8±4.2)nm,Zeta电位分别为-(2.9±0.7)和-(8.1±0.9)mV,且具有良好的物理稳定性。与溶液剂(9-NCSol)相比,微乳能显著降低内酯型水解开环转变为羧酸盐型的速度,有利于提高体内9-NC活性结构(内酯型)的比例。大鼠静脉注射微乳(9-NCME-C和9-NCME-T)和溶液剂(9-NCSol)后血浆中内酯型9-NC的AUC0-∞分别为23072.24,20676.33和8954.97μg·min·L-1。结论自微乳对9-NC内酯型具有显著的体内外保护效应。
Abstract
OBJECTIVE To prepare 9-nitrocamptothecin self-emulsifying microemulsion and investigate the protection effect of self-emulsifying microemulsion on 9-NC lactone form in vitro and in vivo.METHODS Two types of self-emulsifying microemulsion with Cremophor EL and Tween 80 as emulsifier respectively were prepared (SMEDDS-C and SMEDDS-T). Comparing with 9-NC solution, the protection effects of self-emulsifying microemulsion on 9-NC lactone were evaluated. RESULTS When the two kinds of SMEDDS were diluted with saline during the dilution ratio of 1∶20, the diameters of microemulsions were (30.2± 4.6) and (21.8±4.2) nm, and the potentials were -(2.9±0.7) and -(8.1±0.3) mV for 9-NCME-C and 9-NCME-T, respectively. Microemulsion dramatically decreased the conversion rate of lactone form to carboxylate form and increased lactone form proportion. The AUC0-∞ of lactone form were 23 072.24 μg·min·L-1 for 9-NC SMEDDS-C, 20 676.33 μg·min·L-1 for 9-NC SMEDDS-T and 8 954.97 μg·min·L-1 for 9-NC solution after intravenous administration in rats. CONCLUSION The lactone form of 9-NC was significantly protected by self-emulsifying microemulsion.
关键词
9-硝基喜树碱 /
自乳化微乳 /
内酯型 /
静脉注射
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Key words
9-nitrocamptothecin /
self-emulsifying microemulsion /
lactone form /
intravenous injection /
pharmacokinetics
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赵淑欣;吕娟丽;章俊麟;姜娟;王坚成;崔征;张强.
自乳化微乳对9-硝基喜树碱内酯型的保护效应[J]. 中国药学杂志, 2008, 43(16): 1243-1247
ZHO Shu-xin;Lü Jun-li;ZHNG Jun-lin;JING Jun;WNG Jin-cheng;CUI Zheng;ZHNG Qing.
Protection Effect of Self-Emulsifying Microemulsion on 9-Nitrocamptothecin Lactone Form [J]. Chinese Pharmaceutical Journal, 2008, 43(16): 1243-1247
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参考文献
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脚注
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基金
国家自然科学基金资助项目(30430706);天然药物与仿生药物国家重点实验室985Ⅱ期研究基金
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