Study on Preparation and in vitro Release Characteristic of Ursolic Acid/PF 127/TPGS-doxorubicin Mixed Nanomicelles / 中国药房

ABSTRACT

OBJECTIVE： To prepare Ursolic acid （UA）/Pluronic F127 （PF127）/TPGS-doxorubicin （DOX） mixed nanomicelles， and to characterize it and study its in vitro release behavior. METHODS： UA/PF127/TPGS nanomicelles were prepared by thin film hydration method. Using encapsulation efficiency of UA as index， combined with the results of single factor tests， L9（34） orthogonal test was used to optimize drug dosage of UA， molar ratio of PF127 to TPGS， hydration temperature and hydration volume， validation test was performed. On the basis of succinylated TPGS， TPGS-DOX was synthesized and mixed with UA/PF127/TPGS to prepare UA/PF127/TPGS-DOX mixed nanomicelles， the appearance， particle size and critical micelle concentration （PF127/TPGS） were investigated. The drug release behavior was examined by dialysis bag diffusion method. RESULTS： The optimal preparation technology of UA/PF127/TPGS nanomicelles was as follows as drug dosage of UA 8 mg， molar ratio of PF127 to TPGS 3 ∶ 7， hydration temperature 50 ℃， hydration volume 4 mL. Average encapsulation efficiency of UA in nanomicelles was 89.00％ （RSD＝0.43％， n＝3）. The prepared UA/PF127/TPGS-DOX mixed nanomicelles solution was clear with opalescence. The nanomicelles were spherical and uniform in size； average particle size was （115.00±9.42） nm； critical micelle concentration of PF127/TPGS （molecular ratio 3 ∶ 7） was 0.001 3％. The in vitro drug release of UA and DOX in the mixed nanomicelles was significantly slowed down， compared with raw materials or substance control. The drug release process of the two drugs in the nanomicelles conformed to Weibull equation. CONCLUSIONS： UA/PF127/TPGS-DOX mixed nanomicelles are successfully prepared with uniform particle size， good stability and good sustained-release effect.