Formulation, preparation and evaluation of an intravenous emulsion containing Brucea javanica oil and Coix Seed oil for anti-tumor application.

摘要

The purpose of this study was to prepare and evaluate the intravenous emulsion (BCOE) containing Brucea javanica oil (BJO) and Coix seed oil (CSO), which is used in anti-tumor treatment. The formulation and preparation of BCOE were systematically investigated. High-pressure homogenization, particle size distribution, zeta-potential and HPLC were carried out. The pharmacokinetics of the main component, oleic acid, and anti-tumor activity studies about the tumor growth inhibitory ratios (TGIR) and the mortality experiments were also employed to evaluate BCOE in vivo compared with BJO emulsion (BJOE) and CSO emulsion (CSOE) using S180 sarcoma-bearing mice. The final BCOE formulation was 10% (w/v) oils with BJO and CSO 3 : 1, 0.6% (w/v) Lipid E 80, 0.3% (w/v) Pluronic F-68 (F-68), 0.1% (w/v) sodium oleate and 2.5% (w/v) glycerin in water. The preparation conditions involved 70 degrees C for preparing the crude emulsion, 6 cycles for high-pressure homogenization at 500 bar, pH value was adjusted to 8.5 after high-pressure homogenization and 115 degrees C for 30 min in a rotating water bath for sterilization. The pharmacokinetics parameters showed the combination of BJO and CSO may not influence the elimination of BCOE and have no significant difference between BCOE and BJOE or CSOE. The data of TGIR and mortality indicated that BCOE could increase the anti-tumor activity of CSOE and reduced the toxicity of BJOE. The mortality study (BCOE 0, BJOE 63.3%, CSOE 13.3%) showed that BCOE greatly reduced the toxicity of BJOE and CSOE. Therefore, the development and application of BCOE will make an important contribution to anti-tumor therapy.