冰片鸦胆子油纳米乳的制备及对大鼠脑胶质瘤的抑瘤作用研究

Preparation of Borneol and Brucea Javanica Oil Nanoemulsion and Tumor Suppression Effect on Glioma in Rats

关键词:  鸦胆子油  冰片  纳米乳  伪三元相图  脑胶质瘤

Key words:  Brucea javanica oil  borneol  nanoemulsion  pseudo-ternary phase diagrams  glioma

摘要:

目的 筛选和优化冰片鸦胆子油纳米乳处方，制备冰片鸦胆子油纳米乳，并初步考察其对大鼠脑胶质瘤的抑瘤作用。方法 通过柱前衍生化处理，建立GC测定鸦胆子油中油酸含量的分析方法；采用转相法制备冰片鸦胆子油纳米乳；绘制伪三元相图，筛选最佳处方；透射电子显微镜观察外观形态、激光粒度仪测定粒径分布和Zeta电位；构建大鼠脑胶质瘤模型，以瘤重和瘤体积变化为指标，初步考察冰片鸦胆子油纳米乳对大鼠脑胶肿瘤的抑瘤作用。结果 建立了GC测定鸦胆子油中油酸含量的分析方法，筛选冰片鸦胆子油纳米乳最佳处方为油相肉豆蔻酸异丙酯35%，鸦胆子油(含1%冰片)35%，乳化剂Cremopher RH40 18%，Labrasol 12%，纳米乳外观呈圆整球形，平均粒径(47.60±0.57)nm，PDI为(0.22±0.01)，Zeta电位为(-1.06±0.12)mV，载药量(0.424 1±0.005 6)mg·mL^-1。抑瘤实验显示，模型组、鸦胆子油注射剂组、鸦胆子油纳米乳组和冰片鸦胆子油纳米乳组的瘤重分别为(1.32±0.19)，(0.84±0.08)，(0.76±0.06)和(0.57±0.10)g，肿瘤体积分别为(72.2±9.4)，(44.2±5.1)，(42.3±4.9)和(27.9±2.5)mm³，鸦胆子油注射剂组、鸦胆子油纳米乳组和冰片鸦胆子油纳米组的肿瘤抑制率分别为36.49%，42.80%和56.94%。结论 所筛选的最佳处方采用转相法制备冰片鸦胆子油纳米乳，粒径分布均匀，油酸含量较高，稳定性较好。同时冰片鸦胆子油纳米乳对大鼠胶质瘤相对具有较强的抑瘤作用，初步推断冰片可能促进鸦胆子油跨过血脑屏障来提高抑瘤作用。

Abstract:

OBJECTIVE To selecte and optimize the prescription of borneol and Brucea Javanica oil nanoemulsion (BBNE), and to prepare the BBNE, then to investigate its tumor suppression effect on glioma in rats.METHODS Establishing the GC analysis methods to determinate BBNE content by pre-column derivatization; applying the techniques of phase inversion to prepare BBNE; selecting and optimizing the prescription of BBNE by pseudo-ternary phase diagrams; using transmission electron microscope and laser granulometer to investigate the appearance shape, determination of particle size distribution and Zeta potential; building glioma tumor model in rats, and investigate BBNE tumor suppression effect by the index of tumor weight and volume. RESULTS The GC analysis method to determinate BBNE content was established successfully, the best prescription of BBNE was oil phase IPM 35%, Brucea Javanica oil (containing 1% borneol) 35%, emulsifier Cremopher RH 18% and Labrasol 12%; the appearance of nanoemulsion was round and spherical, the average particle size was (47.60±0.57)nm, the PDI was (0.22±0.01), the Zeta potential was (?1.06±0.12)mV, and the drug loading capacity was (0.424 1±0.005 6)mg·mL^-1; tumor inhibition experiments showed that the tumor weight and volume of Saline injection group, Brucea Javanica oil injection group, Brucea javanica oil nanoemulsion group and BBNE group were (1.32±0.19), (0.84±0.08), (0.76±0.06), (0.57±0.10)g and (72.2±9.4), (44.2±5.1), (42.3±4.9), (27.9±2.5)mm³, respectively, and the tumor inhibition rates were 36.49%, 42.80%, 56.94%. CONCLUSION The prescription is very well because the BBNE has uniform particle size distribution, higher drug content and better stability, and that BBNE has better tumor suppression effect on glioma in rat show borneol may promote Brucea Javanica oil across the blood-brain barrier to improve tumor suppression effect preliminarily.