目的 研究白桦脂酸纳米囊泡在小鼠体内的分布情况。方法 从形态、粒径、Zeta电位等方面建立了白桦脂酸纳米囊泡物理表征方法。采用小鼠尾静脉注射给药,用HPLC法测定原料药及纳米囊泡在各组织及血浆中不同时间点白桦脂酸的浓度,并计算靶向参数。结果 白桦脂酸纳米囊泡形态呈圆球形且均匀分散,粒径为140.51 nm,多分散系数(PDI)为22.58%,Zeta电位为-28.8 mV,包封率为90.52%,载药量为8.30%,24 h累积释放度85.33%。与注射原料药组相比,注射白桦脂酸纳米囊泡组小鼠各组织及血浆中药物浓度更高,总药-时曲线下面积(AUC)增加了1.81倍,肝组织的靶向评价指标,峰浓度比(Ce)为3.51、相对摄取率(re)为2.87、靶向效率(te)为1.07。结论 制备的白桦脂酸纳米囊泡粒径小、稳定性好、包封率和载药量较高,符合设计要求。白桦脂酸制成纳米囊泡后可显著提高药物的生物利用度,对肝具备明显的靶向性。
Abstract
OBJECTIVE To study the betulinic acid nanovesicle delivery system, and determine the distribution of the preparation in mice.METHODS A physical characterization method of nanovesicles was established, focusing on the aspects of morphology, particle size, Zeta potential, etc.In the study of tissue distribution of betulinic acid nanovesicles in vivo, mice were injected through the tail vein, and the concentrations of betulinic acid in various tissues and plasma at different time points were determined by HPLC, and the targeting parameters were calculated. RESULTS Betulinic acid nanovesicles shape is spherical and uniformly dispersed. The particle size is 140.51 nm, polymer dispersity index(PDI) is 22.58%, Zeta potential is -28.8 mV, encapsulation efficiency is 90.52%, drug loading is 8.30%. Compared with the injection group, the concentration of betulinic acid nanovesicles in the tissues and plasma of mice in the injection group was higher, the total area under the curre(AUC) increase 1.81 times, and the target evaluation index concentration ratio(Ce) of liver tissue is 3.51, relative tissue exposure(re) is 2.87, targeting efficiency(te) is 1.07. CONCLUSION The results show that the betulinic acid nanovesicles have small particle size, good stability, high encapsulation efficiency and drug loading, and meet the design requirements.The betulinic acid nanovesicle delivery system shows that the preparation of nanovesicles from betulinic acid can significantly improve the bioavailability of drugs and have obvious targeting to liver.
关键词
白桦脂酸 /
纳米囊泡 /
组织分布
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Key words
betulinic acid /
nanovesicles /
tissue distribution
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中图分类号：
R944
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