目的 建立与优化体外脂解模型,并研究灰黄霉素(griseofuvin,GRI)自纳米乳(self-nanoemulsifying drug delivery systems,SNEDDS)体外脂解过程中药物动态分布情况。 方法 以甘油三酯(triglyceride,TG)脂解的程度和速度为指标优化体外脂解模型,采用优化的模型研究甘油三酯的结构及含量对灰黄霉素自纳米乳(GRI-SNEDDS)体外脂解过程中药物在水性胶束相、沉淀相及脂质相动态分布的影响。 结果 优化后体外脂解体系组成:胰脂酶浓度800 U·mL-1,胆盐/磷脂胶束浓度为5/1.25 mmol·L-1,缓冲体系是50 mmol·L-1 Trizma maleate,中链甘油三酯(medium chain triglyceride,MCT)的脂解选择一次性加入5 mmol·L-1Ca2+,而长链甘油三酯(long chain triglyceride,LCT)则是逐步加入0.008 mmol·min-1Ca2+。相同甘油三酯含量下,长链甘油三酯自纳米乳脂解后水性胶束相中灰黄霉素的百分含量比中链甘油三酯自纳米乳高;灰黄霉素自纳米乳中甘油三酯含量增加一倍后,长链甘油三酯自纳米乳脂解后水性胶束相中灰黄霉素的百分含量显著提高了32.4%,而中链甘油三酯自纳米乳仅提高5.7%。结论 甘油三酯的脂解程度和速度与其自身结构、组成及体外脂解体系的组成有关。与非脂解相比,体外脂解后灰黄霉素由单一分散在水相油滴中变为分布在水性胶束相、沉淀相及脂质相,并随油的组成及浓度变化而有所变化。这些研究结果为自纳米乳的吸收机制提供有价值的参考。
Abstract
OBJECTIVE To establish and optimize in vitro lipolysis model, and then to study griseofuvin(GRI)distribution during in vitro lipolysis of self-nanoemulsifying drug delivery systems(SNEDDSs). METHODS The lipolysis rate and extent of triglyceride(TG)were two index for in vitro lipolysis model optimization. The partitioning of GRI into lipolysis phases(aqueous phase, pellet phase, lipid phase) was exploited to investigate the impact of structure and lipid loaded of TG on GRI distribution of SNEDDSs in vitro lipolysis.RESULTS The optimal lipolysis model at the start of the experiment was as follows:800 U穖L-1 Pancreatin extract,5/1.25 mmol稬-1NaTDC/PC micelle and 50 mmol稬-1 Trizma maleate. The addition way of Ca2+ for medium chain triglyceride (MCT) and long chain triglyceride(LCT) were fixed addition 5 mmol稬-1 and continuous addition 0.008 mmol穖in-1, respectively. With the same amount of TG in SNEDDSs, percent content of GRI in aqueous phase of LCT-SNEDDS was higher than MCT-SNEDDS. When TG loaded doubled, GRI in aqueous phase of LCT-SNEDDS significantly increased by 32.4%, and which of MCT-SNEDDS raised only 5.7%, respectively. CONCLUSION The lipolysis rate and extent of TG were correlated with its structure and composition of TG and in vitro lipolysis model. Compared to GRI-SNEDDS without lipolysis, during in vitro lipolysis GRI had transferred to aqueous phase, pellet phase and lipid phase from which was only dispersed in emulsion droplet. And the distribution of GRI during in vitro lipolysis depended on the composition and loading rate of TG in SNEDDS. These results may provide useful references to study the absorption mechanism of SNEDDS.
关键词
自纳米乳给药系统 /
体外脂解模型 /
灰黄霉素 /
动态分布
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Key words
self-nanoemulsifying drug delivery system /
in vitro lipolysis model /
griseofuvin /
drug distribution
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中图分类号：
R944
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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(81373361);广东省自然基金资助项目(S2013020012980)
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